Pathologic fracture of the femur neck as first manifestation of a minute columnar cell carcinoma of the thyroid gland

This case report concerns a 64 year-old woman who presented a pathologic fracture of the femur neck. Histologic examination of the performed bone biopsy disclosed the presence of a carcinomatous metastasis with unusual microscopic features. The site of the primary tumor could be unequivocally determined as being the thyroid gland, as immunostaining of the tumor cells showed positivity with anti-thyroglobulin. The thyroidectomy specimen weighed 149 g, was nodular and partially calcified. Exhaustive microscopic examination finally revealed the presence of a minute columnar cell carcinoma, 0.6 cm in diameter, with obvious vascular invasion. This case illustrates well 1) the usefulness of immunostaining with anti-thyroglobulin in cases of bone metastasis with unusual microscopic features and unknown primary, as well as 2) the aggressiveness of this rare type of carcinoma of the thyroid.     

Striatal dopamine dynamics are altered following an intranigral infusion of iron in adult rats

Exercise has a noted effect on skin blood flow and temperature. We aimed to characterize the normal skin temperature response to exercise by thermographic imaging. A study was conducted on ten healthy and active subjects (age=25.8+/-0.7 years) who were exposed to graded exercise for determination of maximal oxygen consumption (VO2 max), and subsequently to constant loads corresponding to 50%, 70%, and 90% of VO2 max. The skin temperature response during 20 min of constant load exercise is characterized by an initial descending limb, an ascending limb and a quasi-steady-state period. For 50% VO2 max, the temperature decrease rate was - 0.0075+/-0.001 degrees C/s during a time interval of 390+/-47 s and the temperature increase rate was 0.0055+/-0.0031 degrees C/s during a time interval of 484+/-99 s. The level of load did not influence the temperature decrease and increase rates. In contrast, during graded load exercise, a continuous temperature decrease of -0.0049+/-0.0032 degrees C/s was observed throughout the test. In summary, the thermographic skin response to exercise is characterized by a specific pattern which reflects the dynamic balance between hemodynamic and thermoregulatory processes.     

Piecewise exponential survival trees with time-dependent covariates

Survival trees methods are nonparametric alternatives to the semiparametric Cox regression in survival analysis. In this paper, a tree-based method for censored survival data with time-dependent covariates is proposed. The proposed method assumes a very general model for the hazard function and is fully nonparametric. The recursive partitioning algorithm uses the likelihood estimation procedure to grow trees under a piecewise exponential structure that handles time-dependent covariates in a parallel way to time-independent covariates. In general, the estimated hazard at a node gives the risk for a group of individuals during a specific time period. Both cross-validation and bootstrap resampling techniques are implemented in the tree selection procedure. The performance of the proposed survival trees method is shown to be good through simulation and application to real data.     

The Homothorax homeoprotein activates the nuclear localization of another homeoprotein, extradenticle, and suppresses eye development in Drosophila

The Extradenticle (Exd) protein in Drosophila acts as a cofactor to homeotic proteins. Its nuclear localization is regulated. We report the cloning of the Drosophila homothorax (hth) gene, a homolog of the mouse Meis1 proto-oncogene that has a homeobox related to that of exd. Comparison with Meis1 finds two regions of high homology: a novel MH domain and the homeodomain. In imaginal discs, hth expression coincides with nuclear Exd. hth and exd also have virtually identical, mutant clonal phenotypes in adults. These results suggest that hth and exd function in the same pathway. We show that hth acts upstream of exd and is required and sufficient for Exd protein nuclear localization. We also show that hth and exd are both negative regulators of eye development; their mutant clones caused ectopic eye formation. Targeted expression of hth, but not of exd, in the eye disc abolished eye development completely. We suggest that hth acts with exd to delimit the eye field and prevent inappropriate eye development.     

"Tower vertebra": a new observation in sickle cell disease

PURPOSE: We studied the frequency of testicular microlithiasis (TM) in a select group of otherwise healthy infertile men with abnormal semen. METHODS: We reviewed scrotal sonography records of 180 consecutive patients with abnormal semen who were referred for evaluation of male infertility. The pampiniform plexus was evaluated for possible varicocele, and the testes were examined for the presence or absence of intratesticular calcifications and/or masses. Five patients with more than 5 echogenic foci per transducer field in either testis were identified. The medical records and sonograms of this subgroup of patients were analyzed. RESULTS: Of the 180 patients, 5 (2.8%) had TM. Three patients with TM had concomitant small varicoceles; 2 others had a history of testicular maldescent. Two patients eventually became fertile. CONCLUSIONS: Our results indicate a higher than expected frequency of TM in otherwise healthy infertile men. We speculate that the magnitude of hypospermatogenesis in patients with TM is variable and may relate to both the degree of testicular dysgenesis and the presence or absence of concomitant scrotal pathology (eg, scrotal varicocele and cryptorchidism).     

Portal hypotensive effects of DL-028 and prazosin on portal hypertensive rats

The portal hypotensive effects of prazosin and DL-028 (chem- ical name: 3-[[4-(2-methoxyphenyl)piperazin-1-yl]methyl]- 2, 3-dihydroimidazo[1,2-c]quinazolin-5(6H)-one(27b)), a synthetic alpha1-adrenoceptor antagonist, were assessed in portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation in Sprague-Dawley rats. Two weeks after ligation, when the hyperdynamic state was stabilized the rats were anesthetized after an overnight fast and cannulated for measuring mean arterial pressure (MAP), portal venous pressure (PVP), cardiac index (CI) and heart rate (HR). Both DL-028 and prazosin (1, 3.3 and 10 microgram/kg) induced dose-dependent decreases of PVP and MAP after intravenous infusion, with effects lasting for longer than 30 min. The maximum percentage reduction of PVP after DL-028 was 10, 10 and 15%, respectively, for the dosages given (1, 3.3 and 10 microgram/kg), and 5, 12 and 25%, respectively, after prazosin. CI was not changed by either drug. HR was not changed by either drug except DL-028 at 10.0 microgram/kg with a bradycardiac effect. Our results showed that both DL-028 and prazosin reduced PVP in portal hypertensive rats.     

Prothymosin alpha modulates the interaction of histone H1 with chromatin

Prothymosin alpha (ProTalpha) is an abundant acidic nuclear protein that may be involved in cell proliferation. In our search for its cellular partners, we have recently found that ProTalpha binds to linker histone H1. We now provide further evidence for the physiological relevance of this interaction by immunoisolation of a histone H1-ProTalpha complex from NIH 3T3 cell extracts. A detailed analysis of the interaction between the two proteins suggests contacts between the acidic region of ProTalpha and histone H1. In the context of a physiological chromatin reconstitution reaction, the presence of ProTalpha does not affect incorporation of an amount of histone H1 sufficient to increase the nucleosome repeat length by 20 bp, but prevents association of all further H1. Consistent with this finding, a fraction of histone H1 is released when H1-containing chromatin is challenged with ProTalpha. These results imply at least two different interaction modes of H1 with chromatin, which can be distinguished by their sensitivity to ProTalpha. The properties of ProTalpha suggest a role in fine tuning the stoichiometry and/or mode of interaction of H1 with chromatin.     

A cytokine mRNA-destabilizing element that is structurally and functionally distinct from A+U-rich elements

The control of mRNA stability is crucial to the regulation of cytokine expression. We describe here a novel, potent destabilizing element found in the 3' untranslated region of granulocyte colony-stimulating factor mRNA. This element, which appears to require at least one stem-loop structure, we term the stem-loop destabilizing element (SLDE). Functionally equivalent elements appear to also exist in the interleukin 2 and interleukin 6 mRNAs. The SLDE is functionally distinct from the A+U-rich elements, which are also present in these and other cytokine mRNAs, because it destabilizes a chimeric mRNA in a tumor cell line in which A+U-rich elements do not function. In addition, the effect of the SLDE is insensitive to calcium ionophore and is therefore regulated independently of A+U destabilizing elements. The existence of two distinct mRNA-destabilizing elements provides an additional mechanism for the differential regulation of cytokine expression.     

A clinicopathologic study of mucinous gastric carcinoma including multivariate analysis

BACKGROUND: Mucinous gastric carcinoma (MGC) is a rare subtype of gastric adenocarcinoma, and its clinical and pathologic features are still controversial. To clarify the significance of this subtype of carcinoma, the authors conducted a case-control study to investigate the clinicopathologic characteristics of MGC and determine whether this mucin-producing histologic type is associated with a worse prognosis than other gastric carcinomas. METHODS: Twenty-two cases of MGC and 46 patients with nonmucinous gastric carcinoma (NGC) were included. Patients were evaluated on the basis of age, gender, tumor size, location, depth of tumor invasion, histologic differentiation, lymph node involvement, organ metastasis, stage at presentation, surgical curability, adjuvant chemotherapy and radiation therapy. To determine whether the MGC itself was an independent prognostic factor, a multivariate analysis was performed with the Cox proportional hazards model. RESULTS: The MGC patients were found to have larger tumors (P < 0.001), tumors more often located in the upper stomach (P < 0.05), more serosal invasion (P < 0.05), more lymph node involvement (P < 0.05), greater frequency of advanced stage disease (P < 0.01), and lower 5-year survival rates (P < 0.05) than NGC patients. There was no significant correlation between the subtypes of differentiation of MGC and other data, including the prognosis. Multivariate analysis showed that clinically important predictive factors were serosal invasion and disease stage at diagnosis. The mucinous histologic type itself was not an independent factor for poor prognosis. CONCLUSIONS: The overall survival rate for patients with MGC was worse than that for patients with NGC. The poor prognosis was correlated with more advanced stage at diagnosis and more frequent serosal invasion, not with the mucinous histologic type.     

Cellular distribution of pulmonary Mn and CuZn superoxide dismutase: effect of hyperoxia and interleukin-1

Pulmonary superoxide dismutase (SOD) plays an important role in the lung defense against O2 toxicity. We have previously demonstrated that tracheal insufflation of interleukin-1 alpha (IL-1) selectively enhances pulmonary MnSOD and protects rats against O2 toxicity. However, little is known about the cellular distribution of pulmonary MnSOD- and CuZnSOD-specific proteins. We performed immunohistochemistry in plastic sections (2 microns thick) to determine the effects of hyperoxia and IL-1 on the cellular distribution of pulmonary MnSOD and CuZnSOD in rats. MnSOD and CuZnSOD were present in all lung cells. Smooth muscle and endothelial cells appeared to contain higher immunoreactive MnSOD and CuZnSOD proteins than other lung cell types. Exposure of rats to 100% O2 for 24 hr had no effect on the cellular distribution and intensity of pulmonary MnSOD. However, at 50 hr after O2 exposure the intensity of pulmonary MnSOD was reduced. In contrast, tracheal insufflation of IL-1 markedly enhanced the intensity of pulmonary MnSOD in rats exposed to O2 for 50 hr. Neither O2 exposure nor IL-1 insufflation had any apparent effect on the distribution and intensity of pulmonary CuZnSOD. We conclude that IL-1 selectively enhances pulmonary MnSOD and that this effect is manifested in most lung cells, particularly smooth muscle and endothelial cells.