Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Keratoconus is a bilateral noninflammatory corneal ectasia with an incidence of approximately 1 per 2,000 in the general population. It has well-described clinical signs, but early forms of the disease may go undetected unless the anterior corneal topography is studied. Early disease is now best detected with videokeratography. Classic histopathologic features include stromal thinning, iron deposition in the epithelial basement membrane, and breaks in Bowman's layer. Keratoconus is most commonly an isolated disorder, although several reports describe an association with Down syndrome, Leber's congenital amaurosis, and mitral valve prolapse. The differential diagnosis of keratoconus includes keratoglobus, pellucid marginal degeneration and Terrien's marginal degeneration. Contact lenses are the most common treatment modality. When contact lenses fail, corneal transplant is the best and most successful surgical option. Despite intensive clinical and laboratory investigation, the etiology of keratoconus remains unclear. Clinical studies provide strong indications of a major role for genes in its etiology. Videokeratography is playing an increasing role in defining the genetics of keratoconus, since early forms of the disease can be more accurately detected and potentially quantified in a reproducible manner. Laboratory studies suggest a role for degradative enzymes and proteinase inhibitors and a possible role for the interleukin-1 system in its pathogenesis, but these roles need to be more clearly defined. Genes suggested by these studies, as well as collagen genes and their regulatory products, could potentially be used as candidate genes to study patients with familial keratoconus. Such studies may provide the clues needed to enable us to better understand the underlying mechanisms that cause the corneal thinning in this disorder.
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PMID:Keratoconus. 949 73

Growth retardation in children with thalassaemia major is multifactorial. We studied the growth hormone (GH) response to provocation by clonidine and glucagon, measured the circulating concentrations of insulin, insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP3), and ferritin, and evaluated the spontaneous nocturnal (12 h) GH secretion in prepubertal patients with thalassaemia and age-matched children with constitutional short stature (CSS) (height SDS < -2, but normal GH response to provocation). The anatomy of the hypothalamic pituitary area was studied in patients with abnormal GH secretion using MRI scanning. Children with thalassaemia had significantly lower peak GH response to provocation by clonidine and glucagon (8.8 +/- 2.3 micrograms/l and 8.2 +/- 3.1 micrograms/l respectively) than did controls (17.6 +/- 2.7 micrograms/l and 15.7 +/- 3.7 micrograms/l respectively). They had significantly decreased circulating concentrations of IGF-I and IGFBP3 (68.5 +/- 19 ng/ml and 1.22 +/- 0.27 mg/l respectively) compared to controls (153 +/- 42 ng/ml and 2.16 +/- 0.37 mg/l respectively). Seven of the thalassaemic children had a GH peak response of < 7 micrograms/l after provocation. Those with a normal GH response after provocation also had significantly lower IGF-I and IGFBP3 concentrations than controls. Analysis of their spontaneous nocturnal GH secretion revealed lower mean (2.9 +/- 1.77 micrograms/l) and integrated (2.53 +/- 1.6 micrograms/l) concentrations compared to controls (4.9 +/- 0.29 micrograms/l and 5.6 +/- 0.52 micrograms/l respectively). Five of them had mean nocturnal GH concentration < 2 micrograms/l and four had maximum nocturnal peak below 10 micrograms/l. These data denoted defective spontaneous GH secretion in some of these patients. MRI studies revealed complete empty sella (n = 2), marked diminution of the pituitary size (n = 4), thinning of the pituitary stalk (n = 3) with its posterior displacement (n = 2), and evidence of iron deposition in the pituitary gland and midbrain (n = 7) in those patients with defective GH secretion (n = 9). Serum ferritin concentration was correlated significantly with the circulating IGF-I (r = -0.47, p < 0.01) and IGFBP3 (r = -0.43, p < 0.01) concentrations. These data prove a high prevalence of defective GH secretion in thalassaemic children associated with structural abnormality of their pituitary gland.
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PMID:Spontaneous and provoked growth hormone (GH) secretion and insulin-like growth factor I (IGF-I) concentration in patients with beta thalassaemia and delayed growth. 1066 1

To elucidate whether the cause of sexual maturation arrest in thalassaemia is of gonadal or pituitary etiology, 10 males with thalassaemia and delayed puberty and 10 with constitutional delay of growth and pubertal maturation (CSS) were extensively studied. Their spontaneous nocturnal gonadotropin secretion and gonadotropin response to intravenous 100 micrograms gonadotropin-releasing hormone (GnRH) were evaluated. Circulating testosterone concentration and clinical response were evaluated after 3 days, 4 weeks and 6 months of intramuscular administration of human chorionic gonadotropin (HCG) (2500 U/m2/dose). Thalassaemic boys had significantly lower circulating concentrations of testosterone compared to those with constitutional delay of growth and sexual maturation (CSS) at the same pubertal stage. Short- and long-term testosterone response to administrations of HCG was markedly decreased in thalassaemic boys. After 6 months of HCG administration 50 per cent (5/10) of the boys did not show significant testicular enlargement or genital changes. Despite the low circulating concentrations of testosterone, none of the patients had high basal or exaggerated gonadotropin response to gonadotropin releasing hormone (GnRH) stimulation. Luteinizing hormone (LH) peak responses to GnRH were significantly lower as compared to controls. Follicle-stimulating hormone (FSH) peak responses to GnRH did not differ among the two study groups. The mean nocturnal LH and FSH secretion was significantly decreased in all thalassaemic boys as compared to boys with CSS at the same pubertal stage (testicular volume). These data proved that hypogonadotropic hypogonadism is the main cause of delayed/failed puberty in adolescents with thalassaemia major. MRI studies revealed complete empty sella (n = 5), marked diminution of the pituitary size (n = 5), thinning of the pituitary stalk (n = 3) with its posterior displacement (n = 2), and evidence of iron deposition in the pituitary gland and midbrain (n = 8) in thalassaemic patients, denoting a high incidence of structural abnormalities (atrophy) of the pituitary gland. Moreover, in many of the thalassaemic boys, the defective testosterone response to long-term (6 months) HCG therapy denoted significant testicular atrophy and/or failure secondary to siderosis. It appears that testosterone replacement might be superior to HCG therapy in these patients. This therapy should be introduced at the proper time in these hypogonadal patients to induce their sexual development and to support their linear growth spurt and bone mineral accretion.
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PMID:Spontaneous and GnRH-provoked gonadotropin secretion and testosterone response to human chorionic gonadotropin in adolescent boys with thalassaemia major and delayed puberty. 1082 33

The diversity of placental structures in Eutherian mammals is such that drawing generalizations from the definitive forms is problematic. There are always areas of reduced interhaemal distance whether the placenta is epitheliochorial, synepitheliochorial, endotheliochorial or haemochorial. However, the thinning may be achieved by different means. The presence of a haemophagous area as an iron transport facilitator is generally associated with endotheliochorial placentae but is also found in sheep and goats (synepitheliochorial) and in tenrecs and hyaenas (haemochorial). Although similar chorioallantoic placentae are found within families, structure begins to diverge at the ordinal level and there is little correlation at the supraordinal level of phylogeny. Differences in formation and function of the yolk sac provide additional variation. There would appear to be considerable adaptive pressure for development or retention of the haemochorial type of chorioallantoic placenta. This type of placenta has several possible drawbacks including more ready passage of fetal cells to the maternal organism and, should the haemochorial condition be achieved early, oxidative stress. At any rate no animal larger than the human and gorilla has this type of placenta. The endotheliochorial condition is found in animals as large as the bears, manatee and elephants. In addition to the ungulates, the epitheliochorial condition is present in the largest animals with the longest gestation periods, the whales. Considering the length of time since the early stages of mammalian evolution, it is probable that few unmodified structural features are present in any currently surviving mammal. Nevertheless, more complete studies of divergent types of mammalian placenta should help our understanding of mammalian interrelationships as well as placental function.
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PMID:What can comparative studies of placental structure tell us?--A review. 1503

In this work we describe the electrorheology of suspensions consisting of hematite (alpha-Fe2O3) particles dispersed in silicone oil in the presence of large dc electric fields. If an electric field pulse is applied to the systems, it is possible to estimate the time that the electrorheological (ER) fluid takes to reach its final microstructure in the presence of the field. Our results indicate that response times of several seconds are typical, and that this time decreases with the field strength. Conventional shear-rate sweeps indicate the existence of a well-defined dynamic yield stress and a shear-thinning behavior. Interestingly, both the yield stress and the shear-thinning slope alpha [relating the viscosity, eta, and the shear rate, .gamma, as eta=alphagamma(.-b) + eta (infinity)] show a linear dependence on the field strength, E, in disagreement with the E2 dependence often reported. This deviation is associated with changes in the conductivity of the dispersion medium with the field strength. A simple calculation of the interactions present in our ER fluid demonstrates that the ER behavior is entirely controlled by hydrodynamic (proportional to .gamma) and electrical forces (proportional to E). This is confirmed by the collapse of all experimental results in a single master curve when the relative viscosity is plotted against the ratio .gamma/E. Careful attention has been paid in this work to the microstructure of the suspensions in the presence of both shear and electric fields simultaneously: the particles gather themselves on the walls of the electrorheological measurement cell, forming aggregates with cylindrical symmetry, shaped as rings or lamellas of solids. The electric field induced increase in viscosity is the consequence of the balance between two actions: that of the electric field, tending to keep particles together, and that of the shear field, forcing the flow of the liquid phase in the regions between rings or between rings and walls.
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PMID:Structural explanation of the rheology of a colloidal suspension under high dc electric fields. 1671 5

A 43-year-old woman presented with complaints of exfoliation of the skin and mottled pigmentation all over the body, intolerance to sunlight for the last 14 years, and swelling on the lower one-third of the neck for 15 years. She was apparently well until the age of 29 years when she noticed redness on her shins which later progressed to involve the upper limbs, chest, and face. Three months later, she observed multiple, small, brownish plaques over the erythematous areas, which gradually spread to the sun-exposed areas, namely the face, forearms, hands, and nape of the neck. The erythema disappeared within 5 months of onset. The patient experienced redness of the face, intolerance to the sun, and reduced sweating, particularly during the summer. There was no history of bullous eruption, difficulty during deglutition, tremors, or pedal edema. She suffered five miscarriages and, ultimately, was successful in delivering a normal boy who is now 16 years of age. She had menarche at the age of 14 years and her menstrual cycle was regular. There was no history of similar illness in the family. On cutaneous examination, the skin on the face, neck, trunk, buttocks, and limbs was found to be dry, lusterless, thin, and covered with fine scales. Mottled hyperpigmentation was observed all over the body. Atrophy and telangiectasia were seen over the neck (Fig. 1), face (Fig. 2), nape of the neck, upper and lower limbs, back, and chest. Mild erythema was observed over the face, nose, ears, and forearms. The hair on the scalp, eyebrows, axillae, and pubic area was sparse and thin. The teeth were loose and discolored due to caries, and a foul odor emanated from the mouth. The nails were lusterless and centrally depressed. The thyroid gland was enlarged, smooth, nontender, and moved with deglutition. No bruit was heard over it. No ocular abnormality was detected. The patient had a haemoglobin level of 7.6 g%, total serum iron binding capacity of 70 micromol/L (normal, 45-66 micromol/L), and serum ferritin level of 10 microg/L (normal, 15-200 microg/L). Peripheral blood smear showed hypochromic microcytic red blood cells. Total and differential leukocyte counts, erythrocyte sedimentation rate (ESR), blood glucose, serum electrolytes, total and differential serum proteins, liver function tests, blood urea, and microscopic examination of urine and stools were within normal limits. The thyroid profile and complement C3 and C4 levels were within normal limits. Rheumatoid factor, antinuclear factor and LE cells were absent. Abdominal ultrasonogram was normal. Fine needle aspiration cytology from the thyroid gland showed features suggestive of colloid goiter. Skin biopsy revealed thinning of the epidermis, flattening of the rete ridges, and hydropic degeneration of the basal cell layer. The dermis was edematous with dilated capillaries, melanophages, and a band-like mononuclear infiltrate. The sweat glands were reduced in number.
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PMID:Late-onset Rothmund-Thomson syndrome. 1747 79

A total of 176 highlander Ladakhis staying at an altitude of 3445 meters were examined for nail changes. Mean age of the subjects was 22.28 years (range 3-58 years). Koilonychia was seen in 47.16% of the subjects. It was most common during fourth (80.56%) and fifth (80%) decade. Males (49.60%) were slightly more commonly affected than females (41.34%). Soldiers (69.57%) were most commonly affected. Peasant and labourers (64.26%) were also equally affected. Most of the soldiers were also involved in forming during their leave period. Recruits (39.29%) and students (30.30%) were less commonly affected. Right index finger (36.36%), right middle finger (30.68%) and right thumb (29.55%) finger nails were most commonly affected followed by left thumb (13.64%), left index finger (10.23%), right ring finger (8.52%) and left middle finger nails (7.95%). Mean haemoglobin levels in those with or without koilonychia were 14.17 and 14.12 gm % respectively. Chronic hypoxia of high of high altitude causing increased erythropoiesis and depletion of iron stores leads to thinning of nail plate and atrophy of the distal nail bed with superadded mechanical trauma of farming or hard labour is the most likely cause of Ladakhi koilonychia. Dietary iron supplementation as a public health programme should be started in Ladakh to meet the demands of increased erythropoiesis in chronic hypoxic conditions.
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PMID:Ladakhi koilonychia. 1764 38

A 52-year-old black woman presented with a 5-year history of gradual swelling and slowed hair growth involving the vertex and both parietal regions of the scalp. Gradually, the swelling progressed to involve the entire scalp, only sparing a peripheral crown. She reported no history of trauma or medications. Slight pruritus of the involved area was the only accompanying symptom. There was no family history of a similar condition. Her past medical history included surgery for ovarian cysts, 10 years previously, and cholelithiasis. Physical examination revealed diffuse hair thinning and alopecia, more prominent along the vertex and parietal regions (Fig. 1a). There was no evidence of scalp inflammation, scaling, or increased hair fragility. The scalp was mildly tender on palpation and had a boggy, spongy consistency. The hairs which still remained in the involved areas were thin, short, and soft (Fig. 1b). The involved area was slightly hypopigmented when compared with adjacent noninvolved scalp. The rest of the physical examination was within normal limits. No abnormalities of the hair shaft were observed on microscopic examination of several plucked hairs. Laboratory investigations, including a complete blood cell count, blood chemistry, urinalysis, sedimentation rate, antinuclear antibodies, and serologic tests for syphilis, hepatitis B and C virus, and human immunodeficiency virus, were negative. A computed tomography scan of the skull demonstrated diffuse and regular thickening of subcutaneous fatty tissue of the scalp, disclosing a maximum scalp thickness of 15 mm at the vertex (Fig. 2). The biopsy from the vertex revealed a normal epidermis and dermis, with diffuse loss of hair follicles. The most striking feature consisted of a large increase in thickness of the subcutaneous fatty tissue (Fig. 3a). Pre-existing hair follicles were replaced by vertical fibrous tracts of lamellar fibroplasia with no inflammatory infiltrate (Fig. 3b). Adipocytes showed a normal size and shape, but the connective tissue septa, which are normally present separating the subcutaneous tissue into fat lobules, were lacking, and subcutaneous fatty tissue consisted of a continuous and diffuse sheet of mature adipocytes (Fig. 3c). Orcein stain revealed normal contents of elastic fibers with foci of condensation at the sites of disappeared pre-existing hair follicles (Fig. 3d). Colloidal iron and Alcian blue (pH 2.5) stains revealed no mucin deposits.
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PMID:Lipedematous alopecia: an uncommon clinicopathologic variant of nonscarring but permanent alopecia. 1847 57

Nanoscale zerovalent iron (NZVI) particles have recently become subject of great interest in the field of groundwater remediation for their ability to treat a wide variety of organic and inorganic contaminants. However, the field application of this technology is strongly hindered by the lack of stability of NZVI water suspensions. This study demonstrates that highly concentrated NZVI slurries (15g/L) can be stabilized for more than 10 days adding 6g/L of xanthan gum biopolymer. Stability against aggregation and sedimentation was achieved in the range of ionic strength 6 x 10(-3)-12 mM and is mainly due to the formation of a viscous gel characterized by shear-thinning behaviour.
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PMID:Stabilization of highly concentrated suspensions of iron nanoparticles using shear-thinning gels of xanthan gum. 1957 85

Atrophy of dorsal root ganglia (DRG) and thinning of dorsal roots (DR) are hallmarks of Friedreich's ataxia (FRDA). Many previous authors also emphasized the selective vulnerability of larger neurons in DRG and thicker myelinated DR axons. This report is based on a systematic reexamination of DRG, DR and ventral roots (VR) in 19 genetically confirmed cases of FRDA by immunocytochemistry and single- and double-label immunofluorescence with antibodies to specific proteins of myelin, neurons and axons; S-100alpha as a marker of satellite and Schwann cells; laminin; and the iron-responsive proteins ferritin, mitochondrial ferritin, and ferroportin. Confocal images of axons and myelin allowed the quantitative analysis of fiber density and size, and the extent of DR and VR myelination. A novel technology, high-definition X-ray fluorescence (HDXRF) of polyethylene glycol-embedded fixed tissue, was used to "map" iron in DRG. Unfixed frozen tissue of DRG in three cases was available for the chemical assay of total iron. Proliferation of S-100alpha-positive satellite cells accompanied neuronal destruction in DRG of all FRDA cases. Double-label visualization of peripheral nerve myelin protein 22 and phosphorylated neurofilament protein confirmed the known loss of large myelinated DR fibers, but quantitative fiber counts per unit area did not change. The ratio of myelinated to neurofilament-positive fibers in DR rose significantly from 0.55 to 0.66. In VR of FRDA patients, fiber counts and degree of myelination did not differ from normal. Pooled histograms of axonal perimeters disclosed a shift to thinner fibers in DR, but also a modest excess of smaller axons in VR. Schwann cell cytoplasm in DR of FRDA was depleted while laminin reaction product remained prominent. Numerous small axons clustered around fewer Schwann cells. Ferritin in normal DRG localized to satellite cells, and proliferation of these cells in FRDA caused wide rims of reaction product about degenerating nerve cells. Mitochondrial ferritin was not detectable. Ferroportin was present in the cytoplasm of normal satellite cells and neurons, and in large axons of DR and VR. In FRDA, some DRG neurons lost their cytoplasmic ferroportin immunoreactivity, whereas the cytoplasm of satellite cells remained ferroportin positive. Ferroportin in DR axons disappeared in parallel with atrophy of large fibers. HDXRF of DRG detected regional and diffuse increases in iron fluorescence that matched ferritin expression in satellite cells. The observations support the conclusions that satellite cells and DRG neurons are affected by iron dysmetabolism; and that regeneration and inappropriate myelination of small axons in DR are characteristic of the disease.
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PMID:The dorsal root ganglion in Friedreich's ataxia. 1972 77


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