Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent research clearly shows that fusion genes can be microinjected into a pronucleus of an ovum and integrate into the pig genome. Animals with such fusion genes are called 'transgenic'. The percentage of injected ova that developed into transgenic pigs varied among experiments from 0.31% to 1.73%. The percentage of transgenic pigs that expressed the fusion gene ranged from 17% to 100%. Eleven different regulatory sequences have been used for fusion genes transferred into pigs. Some of these regulatory sequences directed strong gene expression, but control over level of expression was inadequate. Other regulatory sequences directed weak expression, but imparted only brief spikes of induced expression. The predominant gene coding sequences transferred were for growth-related hormones. Elevation of growth hormone (GH) in expressing transgenic pigs enhanced plasma concentrations of insulin-like growth factor-I (IGF-I), insulin, and glucose, improved feed efficiency about 15%, and markedly reduced subcutaneous fat compared to nontransgenic siblings. Growth rate was enhanced in some transgenic GH pigs but not in others, possibly due to dietary limits. The 'over-expression' of GH was detrimental to the general health of most transgenic pigs. The most prevalent problems were lethargy, lameness, and gastric ulcers. Gilts that expressed foreign GH genes were anoestrous. Boars that expressed foreign GH genes lacked libido, but their semen was fertile when used by artificial insemination. Six different fusion genes have been transmitted from transgenic founders to progeny. Most of the transgenic pigs that produced progeny transmitted the fusion gene as an autosomal dominant trait to about half of their progeny. Regulatory sequences that will permit full control of gene expression must be developed before the full potential of gene transfer in pigs can be realized.
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PMID:Expression and performance in transgenic pigs. 219 41

We have produced transgenic pigs that harbour structural genes for bovine and human growth hormone (bGH and hGH) ligated to a mouse metallothionein-I (MT) promoter, human growth hormone-releasing factor (hGRF) ligated to the MT or mouse albumin (ALB) promoter, and human insulin-like growth factor-I (hIGF-I) ligated to MT promoter. From 0.31 to 1.03% of microinjected ova developed into transgenic pigs with the various fusion genes. Foreign GH was present in plasma of 61% of the MT-hGH and 89% of the MT-bGH transgenic pigs. Two of 7 pigs with MT-hGRF and all 3 ALB-hGRF transgenic pigs had high concentrations of GRF in their plasma, but plasma concentrations of porcine GH (pGH) were not higher in GRF transgenic pigs than in littermate control pigs. In contrast, plasma concentrations at birth ranged from 3 to 949 ng hGH/ml for MT-hGH transgenic pigs and 5 to 944 ng bGH/ml for MT-bGH transgenic pigs. Presence of the foreign GH depressed endogenous pGH to non-detectable levels. In MT-bGH transgenic pigs, plasma IGF-I was elevated more than 2-fold, plasma glucose was elevated about 30 mg/dl, and plasma insulin was 20-fold higher than in littermate or sibling control pigs. Two lines of pigs expressing the MT-bGH transgene gained 11.1% and 13.7% faster, and were 18% more efficient in converting feed to body weight gain than were sibling control pigs. Expression of the MT-bGH transgene caused a marked repartitioning of nutrients from subcutaneous fat into other carcass components, including muscle, skin, bone and certain organs. The persistent excess hGH or bGH in transgenic pigs was detrimental to general health; lameness, lethargy and gastric ulcers were the most prevalent problems. Gilts that expressed the hGH or bGH transgenes were anoestrous. Germ-line transmission was obtained in 4 of 5 expressing transgenic boars and 4 of 5 nonexpressing transgenic boars and gilts. From 2% to 73% of progeny inherited a transgene from founder transgenics. All transgenic progeny of MT-hGH, MT-bGH and MT-hGRF founder males expressed the transgene if their sire also expressed the gene. The concentration of bGH or hGH in plasma of transgenic progeny was similar to the concentration present in the founder transgenic.
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PMID:Integration, expression and germ-line transmission of growth-related genes in pigs. 221 18

Acromegaly was diagnosed in 14 middle-aged to old cats of mixed breeding. Thirteen (93%) of the cats were male and one was female. The earliest clinical signs in the 14 cats included polyuria, polydipsia, polyphagia, all of which were associated with untreated diabetes mellitus. All developed severe insulin resistance within a few months; peak insulin dosages required to control severe hyperglycemia ranged from 20 to 130 U per day. Other clinical findings weeks to months after diagnosis included enlargement of one or more organs (e.g., liver, heart, kidneys, and tongue) (n = 14), cardiomyopathy (n = 13), increase in body size and weight gain (n = 8), nephropathy associated with azotemia and clinical signs of renal failure (n = 7), degenerative arthropathy (n = 6), and central nervous system signs (i.e., circling and seizures) caused by enlargement of the pituitary tumor (n = 2). The diagnosis of acromegaly was confirmed by demonstration of extremely high basal serum growth hormone concentrations (22 to 131 micrograms/l) in all cats. Computerized tomography disclosed a mass in the region of the pituitary gland and hypothalamus in five of the six cats in which it was performed. Two cats were treated by cobalt radiotherapy followed by administration of a somatostatin analogue (octreotide), whereas two cats were treated with octreotide alone. Treatment had little to no effect in decreasing serum GH concentrations in any of the cats. Eleven of the 14 cats were euthanized or died four to 42 months (median survival time, 20.5 months) after the onset of acromegaly because of renal failure (n = 2), congestive heart failure (n = 1), concomitant renal failure and congestive heart failure (n = 3), progressive neurologic signs (n = 2), persistent anorexia and lethargy of unknown cause (n = 1), the owner's unwillingness to treat the diabetes mellitus (n = 1), or unknown causes (n = 1). Results of necropsy examination in ten cats revealed a large pituitary acidophil adenoma (n = 10), marked left ventricular and septal hypertrophy (n = 7), dilated cardiomyopathy (n = 1), arthropathy affecting the shoulder, elbow, or stifle (n = 5), and glomerulopathy characterized by expansion of the mesangial matrix and variable periglomerular fibrosis (n = 10).
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PMID:Acromegaly in 14 cats. 240 66

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

A male infant with secondary hypothyroidism is described. Within the first month after birth, the patient manifested feeding difficulties, lethargy, persistent jaundice, umbilical hernia, and large anterior and open posterior fontanels. The roentgenogram of the knee joints at 27 days showed absence of the distal femoral epiphyses. His serum thyroid-stimulating hormone (TSH) level was low despite decreased levels of triiodothyronine (T3) and tetraiodothyronine (T4) in serum. Assessment of the hypothalamic-pituitary hormone (TRH) nor growth hormone (GH) responses to L-arginine and insulin, while responses of both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to luteinizing hormone-releasing hormone (LH-RH) and adrenocorticotropic hormone (ACTH) to insulin were within normal limits. The malady of the patient in this case was not detected by newborn screening for congenital hypothyroidism due to the fact that in the Aomori district of Japan thyroid screening involves only the measurement of TSH. Such measurement cannot detect cases of secondary or tertiary hypothyroidism such as our patient. Replacement therapy was initiated at 58 days and his physical and mental development has been regarded as normal since treatment.
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PMID:Congenital secondary hypothyroidism with low serum GH and prolactin levels in a 27-day-old male infant. 628 48

Primary hypothyroidism and partial primary adrenocortical deficiency (isolated glucocorticoid deficiency) were diagnosed in an 8-year-old spayed female boxer dog, presented because of progressive symmetrical truncal alopecia, lethargy, and intolerance to cold. The diagnosis was based upon the combination of low, non-TSH-responsive concentrations of plasma thyroxine and low urinary excretion of corticoids together with high plasma concentrations of ACTH. Normal suppressibility of ACTH concentrations by a low dose of dexamethasone indicated an intact feedback system. Plasma growth hormone levels were elevated, most probably because somatostatin release was depressed by the glucocorticoid deficiency. The dog improved during oral replacement therapy with thyroxine until death ensued after 9 months as a result of intercurrent disease. Autopsy revealed thyroid atrophy and lymphocytic adrenalitis with complete destruction of the zona fasciculata and zona reticularis of the adrenal cortex. The combination of primary hypothyroidism and primary adrenocortical deficiency in this dog is identical to the entity known as type II polyglandular autoimmunity or Schmidt's syndrome in humans. The adrenocortical insufficiency remained confined to glucocorticoid deficiency during the observation period; on no occasion did electrolyte concentrations in the plasma reach values suggestive of mineralocorticoid deficiency.
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PMID:Polyglandular deficiency syndrome in a boxer dog: thyroid hormone and glucocorticoid deficiency. 757 Dec 81

1. The effects of fluparoxan, an alpha 2-adrenoceptor antagonist, on the pharmacodynamic changes induced by clonidine were investigated in this placebo-controlled, double-blind, two-period, cross-over study in 16 healthy male volunteers (aged 19 to 44 years). 2. Subjects received either fluparoxan or placebo, twice-daily for 5 1/2 days (11 doses). One hour after the first and last dose of each treatment period, clonidine (200 micrograms) was infused intravenously over 5 min. 3. Indices of clonidine-mediated pharmacodynamic responses (growth hormone secretion, bradycardia, hypotension, xerostomia and sedation) were taken before and after clonidine infusion. Growth hormone secretion was assessed by quantifying serum growth hormone concentrations; sedation was assessed by both visual analogue scales (VAS) and by a visual psychomotor response meter, measuring critical flicker fusion (CFF). 4. The majority of subjects reported minor adverse events such as lethargy, headache and dry mouth following clonidine infusion. All adverse events were likely to be related to clonidine, as they occurred consistently between treatment groups. Fluparoxan has, however, in previous studies been reported to cause headache and light-headedness. 5. Prior to the clonidine infusion, fluparoxan caused small but statistically significant increases in systolic blood pressure (4 mm Hg) and salivary flow (approximately 30%) after both single and repeated doses. A small increase in heart rate (2 beats min-1) was seen after a single dose which was also statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antagonism of the effects of clonidine by the alpha 2-adrenoceptor antagonist, fluparoxan. 766 82

Stress precipitates depression and alters its natural history. Major depression and the stress response share similar phenomena, mediators and circuitries. Thus, many of the features of major depression potentially reflect dysregulations of the stress response. The stress response itself consists of alterations in levels of anxiety, a loss of cognitive and affective flexibility, activation of the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system, and inhibition of vegetative processes that are likely to impede survival during a life-threatening situation (eg sleep, sexual activity, and endocrine programs for growth and reproduction). Because depression is a heterogeneous illness, we studied two diagnostic subtypes, melancholic and atypical depression. In melancholia, the stress response seems hyperactive, and patients are anxious, dread the future, lose responsiveness to the environment, have insomnia, lose their appetite, and a diurnal variation with depression at its worst in the morning. They also have an activated CRH system and may have diminished activities of the growth hormone and reproductive axes. Patients with atypical depression present with a syndrome that seems the antithesis of melancholia. They are lethargic, fatigued, hyperphagic, hypersomnic, reactive to the environment, and show diurnal variation of depression that is at its best in the morning. In contrast to melancholia, we have advanced several lines of evidence of a down-regulated hypothalamic-pituitary adrenal axis and CRH deficiency in atypical depression, and our data show us that these are of central origin. Given the diversity of effects exerted by CRH and cortisol, the differences in melancholic and atypical depression suggest that studies of depression should examine each subtype separately. In the present paper, we shall first review the mediators and circuitries of the stress system to lay the groundwork for placing in context physiologic and structural alterations in depression that may occur as part of stress system dysfunction.
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PMID:Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states. 1192 Jan 53

Hyperglycemia is seldom described in young patients with pituitary gigantism. Here, we describe the case of a 17-year-old Taiwanese boy who developed depressive mood disorder and diabetic ketoacidosis (DKA) at the presentation of pituitary gigantism. The boy complained of lethargy and dysphoric mood in June 2008. He presented at the emergency department with epigastralgia and dyspnea in January 2009. Results of laboratory tests suggested type 1 diabetes mellitus with DKA. However, serum C-peptide level was normal on follow-up. Although he had no obvious features of acral enlargement, a high level of insulin-like growth factor 1 was detected, and a 75 g oral glucose suppression test showed no suppression of serum growth hormone levels. A pituitary macroadenoma was found on subsequent magnetic resonance imaging. The pituitary adenoma was surgically removed, followed by gamma-knife radiosurgery, and Sandostatin long-acting release treatment. He was then administered metformin, 500 mg twice daily, and to date, his serum glycohemoglobin has been <7%.
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PMID:Pituitary gigantism presenting with depressive mood disorder and diabetic ketoacidosis in an Asian adolescent. 2372 15

Physicians should possess specific diagnostic and pharmacotherapeutic skills in order to recognize symptoms associated with doping use. It is important to be on the alert in athletes and fitness enthusiasts for physical and psychological changes due to use of anabolic steroids such as acne, stretch marks, gynecomastia, signs of acromegaly, irascibility and lethargy. Stimulants such as amphetamines, ephedrine and cocaine lead to fat loss and increased alertness; their main side effects are cardiac problems, behavioural changes and addiction. In addition to anabolic steroids and stimulants, erythropoietin, growth hormone, diuretics and glucocorticoids are regularly used to improve sport performance. In cycling, a biological passport will be used in an attempt to detect doping use. In future, the Olympic motto 'citius, altius, fortius' (faster, higher, stronger) will have ground-breaking consequences for the performance and health of top athletes.
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PMID:[Faster, higher, stronger: knowledge about old and new doping substances]. 2384 31


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