Role of prolactin in developmental differentiation of hypophysiotropic tuberoinfundibular dopaminergic neurons.
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Animals↗
Biomedical subjects
D L Hurley
Publications and source records attributed to D L Hurley.
Detection and treatment of hypothyroidism and Graves' disease.
The clinical presentations of thyroid disorders are often subtle in older adults and may be confused with "normal" aging. To avoid delay in diagnosis, we recommend routine TSH screening of all patients age 60 and older in the primary care practice. With hypothyroidism, pursue treatment cautiously; start with small doses of levothyroxine and closely monitor serum TSH values. When hyperthyroidism is caused by Graves' disease, begin symptomatic therapy with a beta blocker or antithyroid drugs, followed by definitive thyroid ablation with radioiodine. Surgical treatment may be indicated if a goiter causes compressive symptoms.
Aged↗
Thyroid nodular disease: is it toxic or nontoxic, malignant or benign?
The thyroid gland is known to become more nodular with age. The clinical questions in a given patient are whether the nodule(s) is benign or malignant and euthyroid or toxic. Toxic multinodular goiter (MNG) is more common in the elderly than Graves' disease but is not associated with the classic eye or skin findings. Drug therapy is usually effective, but total thyroidectomy may be preferred. Nontoxic MNG is common among older women. Treatment remains controversial because of potential side effects of suppressive therapy. Although thyroid carcinoma is rare, most of the more aggressive tumors are seen after age 50. Fine-needle aspiration and cytologic examination are useful in separating benign from malignant tumors.
Aged↗
The opiate system in invertebrates.
The presence in diverse species of a similar mode of communication, that of a soluble messenger binding to a receptor, raises the question as to whether the specific components of this system are equally widespread. Do invertebrates use the same hormones and receptors as vertebrates do? Invertebrates ranging from unicellular organisms to insects have been shown to contain opiate-like peptides and binding sites, and they exhibit biological responses to opiates. However, critical genetic data are lacking. It is not known how signal systems arise phylogenetically, but it is conceivable that signal molecules that are already present cause the formation of their own receptors from membrane proteins.
Animals↗
Increased hypothalamic somatostatin expression in mice transgenic for bovine or human GH.
Acute studies of GH removal by hypophysectomy or GH replacement in adult rats have shown that GH has a positive influence on its hypothalamic inhibitory hormone somatostatin (SRIH). The present study was undertaken to assess the effect of lifelong exposure to elevated GH on the development and differentiation of SRIH-producing hypothalamic neurons, including comparison of differing GH levels and heterologous species of GH. Expression of somatostatin peptide and mRNA was evaluated using respective immunocytochemistry and in situ hybridization in brains of transgenic mice bearing constructs of either human (hGH) or bovine (bGH) linked to metallothionein (MT) promoter or bGH linked to phosphoenolpyruvate carboxykinase (PEPCK) promoter. Nontransgenic littermates served as controls. All transgenic constructs resulted in high levels of circulating heterologous GH and significantly elevated body weights. Both bGH levels and body weights were higher in PEPCK-bGH than in MT-bGH mice; mean weights were not different between MT-bGH and MT-hGH mice. Numbers of SRIH-immunoreactive neurons in the hypophysiotropic periventricular nucleus (PeN) of transgenic mice showed a two-fold increase (P < 0.01) relative to control animals; the number of SRIH-positive cells in the medial basal hypothalamus (MBH) was comparable for transgenic and control mice. Total SRIH mRNA in situ hybridization intensity also showed a two-fold increase (P < 0.05) in the PeN of all transgenic mice compared with controls, and was not elevated in the MBH. The higher levels of GH produced in PEPCK-bGH transgenic mice led to greater weight gain, but not to greater SRIH expression than in other GH-transgenic mice, suggesting that the increased SRIH cell number and mRNA in the PeN of MT-GH-transgenic mice may represent a plateau of maximal feedback stimulation. The results indicate that lifelong elevated heterologous GH in mice stimulates hypothalamic SRIH expression markedly. It is not known whether this mechanism is direct or indirect via a mediator of GH such as IGF, but the heterologous GH appears to be specific to these hypophysiotropic neurons.
Animals↗
Postnatal reduction in number of hypothalamic tuberoinfundibular dopaminergic neurons in prolactin-deficient dwarf mice.
Mice homozygous for the recessive 'Ames' dwarf mutation have undetectable serum or pituitary prolactin (PRL). Accompanying this pituitary deficiency is a marked reduction of dopamine (DA) and its rate-limiting synthetic enzyme tyrosine hydroxylase (TH) in PRL-regulating tuberoinfundibular hypothalamic neurons. In order to determine whether this deficit in adult Ames dwarf mice is congenital or arises postnatally, brains of dwarf (df/df) and normal (DF/?) littermate mice were assessed for TH immunoreactivity from 7 days through 2 months of age. Numbers of TH-positive neurons were counted in three hypothalamic DA areas: tuberoinfundibular A12, medial zona incerta A13, and anterior periventricular A14. There was an increase in the number of TH-positive neurons between 7 and 21 days of age in A12 and A14, but not in A13, for both DF/? and df/df mice. Between 21 days and 2 months of age, cell numbers were the same in all three areas in DF/? mice and in A13 and A14 in df/df mice. However, A12 TH-positive cell number in dwarfs decreased significantly (p < 0.01) between 21 days and 2 months, and was markedly lower (p < 0.001) in df/df than in DF/? mice at 2 months of age. The results emphasize the specificity of the dopaminergic neuron reduction in the Ames dwarf, which is restricted to the PRL-regulating tuberoinfundibular region. The data also indicate that the dwarf DA/TH deficit has an onset in late postnatal development, suggesting a response to absence of target PRL, rather than a primary hypothalamic effect of the dwarf mutation.
Animals↗
Development of hypophysiotropic neuron abnormalities in GH- and PRL-deficient dwarf mice.
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Animals↗
Prolonged remission of metastatic follicular thyroid carcinoma.
Follicular thyroid carcinoma is associated with an extremely poor prognosis when metastatic lesions occur. Although radioiodine therapy for metastatic disease can extend patient survival for several years, its effect is usually only palliative. Herein we describe a 47-year-old man with metastatic follicular thyroid carcinoma who was in clinical remission for 30 years after surgical and radioiodine treatment of the original disease. To our knowledge, this is the longest reported remission of this disease. Possible reasons for the prolonged survival were "young" age at diagnosis, diploid DNA content of the tumor, skeletal lesions responsive to 131I therapy, and limited pulmonary disease.
Adenocarcinoma, Follicular↗
Growth hormone-releasing hormone peptide and mRNA are overexpressed in GH-deficient Ames dwarf mice.
Hypothalamic expression of growth hormone-releasing hormone (GHRH) was quantified morphologically in dwarf mice which exhibit spontaneous genetic GH absence. Mouse GHRH mRNA was assessed by in situ hybridization; densitometric evaluation of total mRNA in dwarfs showed levels 2.3-fold higher than in phenotypically normal siblings (p < 0.01); assessment of mRNA per neuron by autoradiographic grain counting indicated a 2.5-fold increase per cell in dwarfs (p < 0.005). GHRH peptide was evaluated immunocytochemically using a new mouse-specific antiserum; numbers of neurons containing detectable levels were 3-fold higher in dwarfs (p < 0.005). The increase in GHRH mRNA corroborates that reported previously in the GH-deficient little mouse, and after hypophysectomy in rats; GHRH peptide increase contrasts with previous reports of the effect of acute GH removal by hypophysectomy, in which GHRH levels fell. The results suggest that chronic GH deficiency is accompanied by increased translation as well as transcription of GHRH.
Animals↗
Acquired hypophosphatemia.
This article discusses the regulation of serum phosphorus under normal conditions, focusing on the pathophysiology of acquired hypophosphatemia and its clinical manifestation. In addition, the clinical settings and conditions in which hypophosphatemia is likely to cause severe morbidity are emphasized.
Humans↗
Localization of the tachykinin neurokinin B precursor peptide in rat brain by immunocytochemistry and in situ hybridization.
Tachykinins exert a broad range of actions in the mammalian nervous system. While much is known about the localization of peptides derived from one of the two mammalian tachykinin genes (substance P- and neurokinin A-encoding preprotachykinin), little has been reported on the localization of peptides derived from a second tachykinin gene encoding neurokinin B. Using an antiserum raised against a 30-residue peptide fragment (Peptide 2) of the protein precursor to neurokinin B, we have mapped the distribution of Peptide 2 by immunocytochemistry. Peptide 2 antiserum specificity was determined by western blot analysis (which showed antibody cross-reactivity to a neurokinin B fusion protein from a cloned neurokinin B-encoding complementary DNA) and by the elimination of immunoreactive product in brain tissue sections upon preabsorption with a 10 microM concentration of Peptide 2 peptide. In addition, we report on the distribution of neurokinin B-messenger RNA with a full-length complementary RNA probe to localize cells that express the neurokinin B precursor. Peptide 2 immunoreactivity and neurokinin B-messenger RNA-positive cells were found, in some instances, paralleling the distribution of substance P and in other cases existing separately from substance P. Peptide 2 immunoreactivity as well as neurokinin B-messenger RNA-positive cells were found in the main olfactory bulb, cortex, olfactory tubercle, nucleus accumbens, hippocampus, bed nucleus of the stria terminalis, amygdala, medial habenula, periaqueductal gray, superior and inferior colliculus, and nucleus of the spinal trigeminal tract. Whereas substance P is found throughout the rat brain, neurokinin B appears to be partitioned more to forebrain than to brainstem structures. The marked differences in the distribution of both tachykinins in the rat central nervous system suggests that neurokinin B may play an important role in olfactory, gustatory, visceral, and neuroendocrine processing of information.
Amino Acid Sequence↗
Fatal fungal endarteritis caused by Bipolaris spicifera following replacement of the aortic valve.
A 73-year-old man presented to our hospital 5 months after a porcine replacement of an aortic valve with persistent fevers, meningoencephalopathy, and progressive renal failure; evidence of systemic emboli was found subsequently. The results of an exhaustive evaluation were negative except for two of 23 blood cultures that were performed; each of these two cultures yielded one colony of Drechslera species (now known as Bipolaris) on one plate. Autopsy revealed a fungal vegetation (9.5 x 3.2 x 3.0 cm) in the ascending aorta that arose from suture material 1.0 cm distal to the aortic valve. Mycologic evaluation of the isolate revealed that it was Bipolaris spicifera.
Aged↗
Hypothalamic preprosomatostatin messenger ribonucleic acid expression in mice transgenic for excess or deficient endogenous growth hormone.
The influence of altered endogenous GH status on somatostatin (somatotropin release-inhibiting hormone; SRIF) gene expression was studied in two transgenic mouse models. Transgenic dwarf mice carried the rat GH gene promoter fused to the diphtheria toxin A-chain gene, placing toxin expression under GH promoter control. As a result, the toxic product of the transgene ablated all GH-expressing cells, resulting in undetectable circulating GH, reduced weight (10.6 +/- 1.0 g for transgenic dwarfs vs. 29.5 +/- 1.7 g for controls; P less than 0.001), and no detectable somatotrophs. Transgenic giant mice contained a construction combining a widely expressed metallothionein promoter and the human GH-releasing hormone (hGHRF) structural gene. Transgene expression of hGHRF resulted in overproduction of endogenous mouse GH in the anterior pituitary and weight increases (42.7 +/- 2.7 g for giants vs. 29.5 +/- 1.7 g for controls; P less than 0.005). Using in situ hybridization, control mice, transgenic dwarfs, and transgenic giants were compared for levels of prepro-SRIF mRNA. Hybridization signal intensities for prepro-SRIF mRNA were similar in transgenic dwarfs to those in littermate nontransgenic mice in non-GH-regulating regions of the brain, such as cortex (control, 31 +/- 2 U; dwarf, 27 +/- 2) and reticulothalamic nucleus (control, 41 +/- 2 U; dwarfs, 39 +/- 3). Transgenic giant mice had hybridization intensity of SRIF mRNA similar to that of normals in cortex (controls, 31 +/- 2 U; giant, 27 +/- 1) and reticulothalamic nucleus (controls, 41 +/- 2 U; giant, 40 +/- 4). In the GH-regulating neurons of the anterior periventricular hypothalamus (PeN), prepro-SRIF mRNA signal in transgenic dwarf mice decreased to 60% of that in controls (88 +/- 13 U for dwarfs vs. 147 +/- 17 U for controls; P less than 0.01), although the numbers of mRNA-expressing cells in the PeN were not different between the transgenic dwarfs and controls (dwarfs, 69 +/- 6 cells; controls, 72 +/- 4 cells). The transgenic giant mice had 230% higher prepro-SRIF mRNA signal than control mice in the PeN (343 +/- 30 U in giants vs. 147 +/- 17 U in controls; P less than 0.001). Again, the numbers of mRNA-expressing cells were not different in giants (57 +/- 9) and normals (72 +/- 4). These results suggest that while the lack of endogenous GH is accompanied by a slight decrease in transcriptional expression of SRIF in the PeN, the overproduction of endogenous GH greatly stimulates hypothalamic SRIF steady state mRNA levels.
Animals↗
Hypothalamic dopaminergic neurons in transgenic dwarf mice: histofluorescence, immunocytochemical, and in situ hybridization studies.
Spontaneous dwarf mice, in which both growth hormone (GH) and prolactin (PRL) are undetectable, are severely deficient in the PRL-inhibiting catecholamine dopamine (DA), as well as its synthetic enzyme, tyrosine hydroxylase (TH), in the basal hypothalamus (Phelps et al., Cell Tissue Res., 240:19-25, 1985; Phelps, Brain Res., 416:354-358, 1987). In contrast, transgenically constructed dwarf mice (Behringer et al., Genes Dev., 2:453-461, 1988) show complete ablation of pituitary GH cells, but PRL cells are retained at a level of approximately 10% of normal. In order to determine the feedback effect of this reduced, rather than absent, PRL on hypothalamic DA neurons, brains of transgenic dwarf mice were examined for catecholamine transmitters by histofluorescence, for the synthetic enzyme TH by immunocytochemistry, and for TH mRNA expression by in situ hybridization. DA histofluorescence in transgenic dwarfs was comparable to that of normal littermate mice in nonpituitary regulating areas (perikarya of zona incerta [A13] of hypothalamus and in midbrain substantia nigra area [A9]). Arcuate nucleus (A12) DA neurons that inhibit PRL secretion, however, showed dim to absent fluorescence in perikarya and in external median eminence terminals in dwarfs. There were reduced (P less than 0.05) numbers of A12 TH-immunoreactive neurons in transgenic dwarfs, to approximately 60% of those in normal mice. In contrast, TH-positive neurons in other hypothalamic areas (A13, A14) had average populations equivalent to those in normal mice. Quantification of TH mRNA abundance by in situ hybridization using both image analysis of hybridization over the arcuate nucleus, and grain counts per individual A12 cell in this nucleus, indicated that relative mRNA levels were the same in normal and transgenic dwarfs. The observations indicate that reduction in pituitary PRL is accompanied by defective expression in hypothalamic tuberoinfundibular neurons, which is severe at the DA neurotransmitter level, significant regarding observable TH immunoreactivity, and undetectable with regard to TH mRNA expression. Collectively, the findings suggest that posttranscriptional processes are involved with the mediation of PRL feedback upon hypothalamic neurons. Technically and quantitatively, the report presents the feasibility of simultaneous evaluation of transmitter histofluorescence, synthetic enzyme immunocytochemistry, and mRNA expression in individual animals.
Animals↗
Women, alcohol and incest: an analytical review.
This study examines the historical treatment of two phenomena that impact negatively on the lives of millions of women--incest and alcoholism--and explores the similarities in characteristics of alcoholic women and women with histories of incest. Prior to the early 1980s, incest histories were rarely mentioned in the literature on alcohol. Similarly, the literature on incest makes only passing references to alcohol abuse among adolescent and adult survivors. Hence, formal research comparisons between the alcoholic woman and the incest-surviving woman are lacking. The purpose of this study is not merely to illustrate the similarities between the alcoholic woman and the incest-surviving woman, but also to present a persuasive argument that multidisciplinary research efforts are essential in order to promote more effectively the identification, diagnosis and treatment of women who suffer both alcoholism and incest. To accomplish these goals, this study presents parallel reviews of (1) women and alcohol and (2) women and incest, then develops a comparative profile of the alcoholic woman and the incest-surviving woman. Additionally, the relatively sparse information on the alcoholic incest-surviving woman is reviewed. This study points to the need for further research in order to address the compelling question that emerges: Why do some incest-surviving women become alcoholic while others do not?
Alcoholism↗
Disseminated histoplasmosis with bilateral adrenal enlargement: diagnosis by computed tomography-directed needle biopsy.
Disseminated histoplasmosis is a rare and potentially fatal disease caused by the dimorphic soil fungus Histoplasma capsulatum. We describe a 67-year-old man with diabetes who presented with a 6-month history of fever, weight loss, and mental deterioration; using computed tomography (CT), we found hepatosplenomegaly and bilateral adrenal masses. CT-directed adrenal biopsy showed yeast forms consistent with H capsulatum. Therapy with ketoconazole was accompanied by adrenal insufficiency (treated successfully with prednisone and fludrocortisone) and produced an excellent therapeutic response. We address the differential diagnosis of bilateral adrenal enlargement, and we discuss the clinical features, diagnosis, and treatment of disseminated histoplasmosis, a disease that includes parts of the Southwestern United States in its endemic region.
Adrenal Glands↗
Fatal hypernatremia from exogenous salt intake: report of a case and review of the literature.
Hypernatremia is a common electrolyte disturbance, most often caused by volume depletion. Hypernatremia due to sodium excess occurs less frequently, and fatal hypernatremia solely from ingestion of table salt is rare. We describe a 41-year-old man who had seizures and hypernatremia after ingestion of a supersaturated salt water solution intended for gargling. He had consumed approximately a third cup of table salt (approximately 70 to 90 g of salt or 1,200 to 1,500 meq of sodium). His initial serum sodium concentration was 209 meq/liter. Hypotonic fluid therapy was given to provide free water and to correct the hypernatremia gradually. Our patient, however, failed to recover from the initial insult and died 3 days later. Review of the literature revealed 10 adult and 20 pediatric cases of hypernatremia attributable to exogenous intake of salt. The type of therapy (fluid or peritoneal dialysis), the type of fluid used, and the rate of correction of hypernatremia did not influence survival. The age of the patient and the initial serum sodium concentration were the most important prognostic indicators. Both very young patients and those with lesser degrees of hypernatremia had a better rate of survival than did other patients. In addition, our review illustrates the surprisingly small amount of salt that can cause severe hypernatremia and the danger of using salt or saline as an emetic.
Adult↗
Long-term parenteral nutrition and metabolic bone disease.
Home parenteral nutrition has prevented malnutrition in patients who cannot maintain adequate nutrition by enteral feedings alone. The risk of bone and mineral abnormalities in these patients is significant for several reasons. Pre-existing skeletal disease can occur from factors known to affect the population at large as well as from malnutrition, malabsorption, and corticosteroid use related to the underlying disease process. Long-term use of infused nutrients and potential toxins can further alter bone turnover. Hypercalciuria is frequently present during HPN, yet its etiology is poorly defined. Parenteral nutrition admixture concentrations of calcium, phosphorus, protein, sodium, and dextrose may all play a role. Any development of acidosis can certainly aggravate hypercalciuria, which may be an indirect marker of abnormal bone turnover. Although increased protein intake can promote the development of acidosis-induced calciuresis, infused phosphorus and acetate can help reduce calcium excretion. Parenteral nutrition contamination by aluminum can cause a spectrum of osteomalacic bone disease similar to aluminum-associated changes seen in renal failure patients. Even with recent attempts to remove aluminum from the parenteral admixture, low-turnover bone disease can still occur. At present, HPN-related bone disease is a poorly understood entity because of its multifaceted nature. Patients receiving long-term parenteral nutrition should be considered to have an increased risk for the development of metabolic bone disease. Early monitoring for and treatment of bone disease should be considered in all patients receiving HPN.
Aluminum↗