Normal deposition of brain iron in childhood and adolescence: MR imaging at 1.5 T

Magnetic resonance (MR) images of the brain in 285 patients between the ages of 2 and 25 years were retrospectively studied to determine the appearance of brain iron accumulation. The globus pallidus, red nucleus, substantia nigra, and dentate nucleus were evaluated with long TR/TE (repetition time/echo time) spin-echo sequences and staged. All four regions in most patients were initially hyperintense compared with white matter (stage I) before becoming isointense (stage II) and subsequently hypointense (stage III). The globus pallidus was the first to reach stage III, the red nucleus and substantia nigra were next, and the dentate nucleus was last. In general, decreased signal intensity (stage III) was not seen in these regions in patients less than 10 years old; in most patients it was seen by age 25 years. The dentate nucleus decreased in signal intensity more slowly and inconsistently; only one-third of patients had reached stage III by age 25 years. The temporal sequence of normal iron deposition as detected with MR imaging is helpful not only in the diagnosis of known iron-deposition diseases but also in the detection of iron-related pathologic changes.     

Osteogenesis imperfecta: changes in noncollagenous proteins in bone

The noncollagenous proteins osteonectin, bone sialoprotein, osteocalcin, the small proteoglycan decorin (PG II), and alpha 2-HS glycoprotein (which is synthesized in the liver but highly concentrated in bone) were measured in extracts of cortical bone from 3 type I, 2 type II, 8 type III and 13 type IV patients with osteogenesis imperfecta (OI) and from 7 control subjects. Osteonectin was found to be reduced in the bone of all OI patients. The bone from severely affected type III OI patients contained the lowest levels of osteonectin. In contrast, bone sialoprotein was found to be elevated in the bones of OI patients. The highest levels were found in individuals classified as type IV patients. Osteocalcin and alpha 2-HS glycoprotein concentrations were increased in all OI patients. Decorin levels were not significantly altered in OI bones compared to controls. These changes in the concentrations of the noncollagenous proteins may contribute to the fragility of the OI bone by interfering with complete mineralization and/or normal tissue architecture.     

Low concentrations of the histone deacetylase inhibitor, depsipeptide (FR901228), increase expression of the Na(+)/I(-) symporter and iodine accumulation in poorly differentiated thyroid carcinoma cells.

Thyroid carcinoma accounts for the majority of deaths from endocrine cancers. A major cause of treatment failure is the inability to trap iodine. Chemotherapeutic agents with differentiating properties have been tried in an attempt to increase iodine uptake. We examined the ability of the novel histone deacetylase (HDAC) inhibitor, depsipeptide (FR901228), to modulate the expression of thyroid-specific genes. Four cell lines, two derived from follicular thyroid carcinomas (FTC 133 and FTC 236) and two derived from anaplastic thyroid carcinomas (SW-1736 and KAT-4) were used. In these four cell lines, a very low concentration of depsipeptide (1 ng/mL) increased histone acetylation and expression of both thyroglobulin and the Na(+)/I(-) symporter messenger RNAs. After 3 days, messenger RNA levels approached those of a normal thyroid control. Depsipeptide induced increases in (125)I accumulation indicated that a functional Na(+)/I(-) symporter protein was induced. Transient transfections indicate that the effects are mediated at least in part by a trans-activating factor. These in vitro results suggest that depsipeptide or other histone deacetylase inhibitors might be used clinically in thyroid carcinomas that are unable to trap iodine as an adjunct to radioiodine therapy.     

Acid phosphatase activity in mononuclear phagocytes and the U937 cell line: monocyte-derived macrophages express tartrate-resistant acid phosphatase

Tartrate-resistant acid phosphatase (TRAcP) is used as a marker for osteoclasts, which are believed to be derived from phagocytic cells or phagocyte stem cell precursors. To further investigate the relationship between monocytic phagocytes and osteoclasts, acid phosphatase (AcP) activity was measured by three different techniques in human peripheral blood monocytes, monocyte-derived macrophages, and the U937 cell line. We found that cytochemistry and gel electrophoresis led to similar results, but that the colorimetric assay was inconsistent. Normal human peripheral monocytes expressed both tartrate-sensitive and -resistant AcP. In culture these cells formed polykaryons and expressed TRAcP activity that was further identified as an isoenzyme associated with bone tissue. In contrast, the U937 cells did not express TRAcP activity as measured by gel electrophoresis. Both U937 cells and monocytes possess material that interferes with interpretation of the colorimetric assay of AcP. The presence of TRAcP in monocyte-derived macrophages further supports the relationship between phagocytic cells and bone osteoclasts.     

Risk factors in age-related maculopathy complicated by choroidal neovascularization

We evaluated previously reported and hypothesized risk factors for the development of age-related maculopathy (ARM) in a case-control study. We compared 26 patients with documented disciform scarring or choroidal neovascularization with 23 age- and sex-matched controls. Systolic and diastolic blood pressure, smoking history, glucose, lipoprotein profiles, and serum levels of vitamins A, C, and E did not differ significantly between the two groups. Statistically significant associations (P less than 0.05) identified by univariate analysis include degree of dermal elastotic degeneration in sun-exposed and sun-protected skin, white blood count, increasing age and small posterior lenticular opacities. Using an interactive multivariate model, only extent of elastosis in sun protected dermis, age and white blood count were predictive (Mult R = 0.652, P less than .001). Our data support the concept of a multifactorial etiology of ARM but suggest that generalized increased susceptibility of elastic fibers to photic or other degenerative stimuli is a new and important risk factor for choroidal neovascularization.     

Haptoglobin from psoriatic patients exhibits decreased activity in binding haemoglobin and inhibiting lecithin-cholesterol acyltransferase activity

Objective The aim of this work was to assess whether psoriasis is associated with phenotype prevalence and altered activity of haptoglobin (Hpt). Background Hpt is a plasma acute‐phase glycoprotein, displaying in humans three phenotypes. Phenotype prevalence or structure modification of Hpt was associated with several diseases. The Hpt main function is to bind and carry to the liver free haemoglobin for degradation and iron recycling. Hpt was recently found able to bind the apolipoprotein A‐I (ApoA‐I), thus impairing its stimulation on the activity of the enzyme lecithin‐cholesterol acyl‐transferase (LCAT). Study design Hpt was isolated from patients with psoriasis vulgaris, and its activity in haemoglobin or ApoA‐I binding and LCAT inhibition was compared with that of normal protein. Methods Two affinity chromatography steps, the first using resin‐coupled haemoglobin and the second anti‐Hpt antibodies, were used to purify Hpt. The protein phenotype was assessed by electrophoresis. Binding experiments were performed by Enzyme‐linked immunosorbent assay with stationary haemoglobin or ApoA‐I, Hpt in solution and anti‐Hpt antibodies for detection of bound Hpt. Standard LCAT assays were carried out in the presence of Hpt purified from patients or healthy subjects. Results Phenotype prevalence of Hpt in psoriasis was not found. After affinity chromatography by haemoglobin, albumin and ApoA‐I were routinely found heavily contaminating only Hpt from normal subjects. Isolated Hpt from patients had lower activity than normal protein in both haemoglobin binding and LCAT inhibition. Conclusions In psoriasis, Hpt displays some structure modification(s), which might be associated with the protein function in the disease.     

Expression of bone sialoprotein (BSP) in developing human tissues

Summary Bone sialoprotein (BSP) and its messenger RNA were localized in developing human skeletal and nonskeletal tissues by means of immunohistochemistry andin situ hybridization. Both protein and mRNA were found in mature, bone-forming cells but not in their immature precursors. In addition, osteoclasts displayed positive immunostaining and high densities of autoradiographic grains byin situ hybridization experiments. BSP was expressed in fetal epiphyseal cartilage cells, particularly in hypertrophic chondrocytes of growth plates. Though neither the protein nor the mRNA were identified in a variety of other connective and nonconnective tissues, an unexpected finding was the expression of BSP in the trophoblast cells of placenta. These findings show that BSP is primarily an osteoblast-derived component of the bone matrix expressed at late stages of differentiation. We have also found that osteoclasts produce BSP, possibly as a mediator of cell attachment to bone.     

Ectopic ureter and ureterocele: their varied sonographic manifestations

The sonographic examinations of four patients with simple ectopic ureters and 11 with ectopic ureteroceles were reviewed to determine distinguishing characteristics. Ectopic ureters, in cases of extreme dilatation and tortuosity, sometimes mimic multiseptated, cystic abdominal masses. However, the proximal portions of some severely dilated ureters are surprisingly small. Ectopic ureters sometimes indent the lower vesical wall, simulating a ureterocele. Ectopic ureteroceles are dynamic structures, changing in shape and size according to intravesical pressure. The lower pole of a duplex kidney may be difficult to detect because of displacement by the dilated upper renal pelvis and ureter. The renal parenchyma associated with an ectopic ureter may be equally difficult or impossible to find because of diminutive dysplasia or, less commonly, acquired atrophy. Dysplasia is characterized sonographically by highly echogenic parenchyma, lack of corticomedullary differentiation, and occasionally massive enlargement by cysts. Ectopic ureters and ureteroceles can be identified by fetal sonography.     

Osteomyelitis: detection with US

To evaluate the role of ultrasound (US) in the detection of osteomyelitis, the authors prospectively studied 48 patients clinically suspected of having osteomyelitis. A sonographic diagnosis was made if fluid was seen directly in contact with bone, without intervening soft tissues. Twelve of the 48 patients were subsequently found to have osteomyelitis. In 10 of them, US demonstrated abnormal fluid adjacent to the bone. This fluid was thought to represent an inflammatory exudate dissecting in a subperiosteal and/or extraperiosteal location. Eight of the 48 patients had soft-tissue fluid collections. The rest of the patients either had no abnormalities or had cellulitis. The authors conclude that US can be useful in the detection of osteomyelitis.