MKK4 and metastasis suppression: a marriage of signal transduction and metastasis research

MAP kinase kinase 4 (MKK4) is a member of the stress-activated protein kinase (SAPK) signaling cascade and is involved in the regulation of many cellular processes. We have recently demonstrated a functional role for MKK4 in the suppression of metastases. In this review, we discuss the established cellular and biochemical functions of MKK4, as well as a new function for MKK4 as a metastasis suppressor gene. Because of the importance of signaling studies to this translational work, a detailed example of the strategy and tools that can be employed to define the biochemical mechanism of MKK4-mediated metastasis suppression is presented. Finally, the potential therapeutic utility of these findings is discussed.     

Diagnostic procedure in osteodystrophia deformans Paget

Simultaneous scintigraphic and X-ray examination has been evaluated in 30 patients with Paget's disease for estimation of extension and activity of the disease. Scintigraphy produces a comprehensive picture of the pathophysiologic condition. When compared with X-rays the procedure is more economic with regards to cost, time and radiation dosage. Therefore, the use of radioisotopes for evaluation of the skeleton is strongly recommended for follow-up examination in Paget's disease.     

Muscarine receptor types mediating autoinhibition of acetylcholine release and sphincter contraction in the guinea-pig iris

Summary The potencies of several muscarine receptor antagonists in blocking either the autoinhibition of acetylcholine release or the muscarinic contraction of the sphincter muscle upon acetylcholine release were investigated in the guinea-pig iris. The agonist at pre- or postjunctional muscarine receptors was acetylcholine released upon field stimulation (5.5 Hz, 2 min) of the irides preloaded with ¹⁴C-choline. The stimulation-evoked ¹⁴C-overflow was doubled in the presence of atropine 0.1 mol/l but unaffected by the agonist (±)-methacholine (50 mol/l). Thus, under the present stimulation conditions, the autoinhibition of acetylcholine release on the guinea-pig iris cholinergic nerves was nearly maximally activated. Isotonic contractions of the irides upon field stimulation consisted of a rapid, atropine (0.1 mol/l). peak phase followed by a sustained contraction which involved a cholinergic and a non-cholinergic stimulation of the sphincter muscle. The M₂-selective antagonists methoctramine (10 mol/l) and gallamine (100 µmol/l). increased both the ¹⁴Goverflow and the peak contractions evoked by field stimulation. In contrast, the M₃-selective antagonist hexahydrosiladifenidol (0.1–10 mol/l) failed to affect the evoked ¹⁴C-release but concentration-dependently (1–10 mol/l) reduced the iris contractions. Pirenzepine (10 mol/l) enhanced the evoked ¹⁴C-overflow and inhibited the peak contractions (0.1–10 mol/l; maximal effect at 10 mol/l). The low potency of the antagonist at both receptor sites indicates that an M₁ muscarine receptor is not involved. The results are consistent with the idea of M₂ muscarine receptors mediating autoinhibition of acetylcholine release in the guinea-pig iris and M₃-like receptors inducing the contraction of the sphincter muscle. Send offprint requests to I. T. Bognar at the above address     

Rheumatic and Musculoskeletal Diseases (RMDs) Public Awareness Program of Georgia 2019–2020

Clinical Rheumatology - The program’s goal is to launch the platform of positive perspectives for people who are suffering from/working in rheumatic and musculoskeletal diseases through the...     

A cross-sectional study of newborns over a 20-year period in Szeged,Hungary

Objective: Records of metric data of birth, serve not only the medical needs of the newborn baby, but are also indicators to assess the status of public health.

Methods: This is a retrospective study of 4946 newborns (singleton: 2508 boys and 2365 girls) born in 1989 and in 2009 at the Department of Obstetrics and Gynaecology of the University of Szeged. We aimed as to compare and map the metrical changes over 20 years, and to describe the averages of four body parameters of the normal birth weight (2500–4000?g) subgroup (3993 singleton babies) in both years. Statistical analysis was performed with SPSS 17.0.

Results: In 1989, the mean birth weight was 3223.770?±?559.595?g, birth length 49.551?±?2.729?cm, chest circumference 32.181?±?2.231?cm, and head circumference 34.122?±?1.688?cm. In 2009, the birth weight was 3309.673?±?582.630?g, birth length 49.515?±?2.658?cm, chest circumference 32.736?±?2.392?cm and head circumference 33.854?±?1.768?cm. The mean birth weight, chest circumference and the maximum value of birth weight have thus increased. The mean maternal age shifted to 30.21?±?4.863 years, which is an increase of 3.57 years in 20 years.

Conclusion: The body parameters of newborns changed significantly between 1989 and 2009. As underlying causes changes in eating habits and lifestyle of the mother are to be mentioned.     

Fenestration of the middle cerebral artery and aneurysm at the site of the fenestration

Abstract

The authors report the case of a patient who presented a ruptured aneurysm of the anterior communicating artery and an unruptured aneurysm of the middle cerebral artery arising at the site of a fenestration of the MCA. The fenestration was undiagnosed on the preoperative angiogram but discovered during the surgery carried out for clipping of the aneurysms. In the literature, cases of fenestration of the MCA are sporadically reported and are incidental findings; an aneurysm may be associated on an artery other than the fenestrated MCA; an aneurysm arising at the site of the MCA fenestration is a very rare occurrence.     

Ventriculosubgaleal shunt in the treatment of posthemorrhagic and postinfectious hydrocephalus of premature infants

Purpose

The aim of the study was to compare the characteristics of ventriculosubgaleal shunts during the clinical course of posthemorrhagic and postinfectious hydrocephalus in the neonatal period.

Patients and methods

The study comprised 102 premature babies in whom subgaleal shunt was consecutively inserted between 2006 and 2011. Seventy-two patients had posthemorrhagic hydrocephalus (mean gestational age 27.3?±?2.1 weeks, mean birth weight 1,036.9?±?327.7 g, mean age at insertion 51.4?±?56.2 days) and 30 patients were operated postinfectiously (27.5?±?2.2 weeks, 1,064.7 g?±?310.7 g, 115.9?±?47.8 days).

Results

The mean survival of subgaleal shunts was 87.9 days for the posthemorrhagic group and 75.6 days for the postinfectious group. Only six infants (8.3 %) did not need ventriculoperitoneal shunts later, all posthemorrhagic. There were meaningful differences between two groups with regard to ventriculosubgaleal shunt-related infections (8.3 % in posthemorrhagic versus 20.0 % in postinfectious) and shunt revision rate (6.9 % in posthemorrhagic versus 13.3 % in postinfectious), but these were not statistically significant. The need of ventriculoscopic procedures was notably more frequent in postinfectious group (1.4 versus 23.3 %).

Conclusion

In premature infants with ventriculomegaly, the subgaleal shunt is an effective temporary diversion tool. The complications were less with posthemorrhagic than with postinfectious hydrocephalus. With previous severe infections of prematures, the risk for complications regarding infection and obstruction will be 2.75 and 2.06 (odds ratios) times higher and more frequent need of ventriculoscopic procedures should be considered (odds ratio 21.6).     

Pathophysiological characterization of drug hypersensitivity to tribenoside

Background

Tribenoside is a semisynthetic sugar derivative that is mainly indicated for treatment of chronic venous insufficiency. Up to 10% of patients treated by tribenoside can suffer from skin side effects. The adverse effects usually present as angioedema, urticaria, or maculopapular exanthema. The pathophysiology of the reaction has not as yet been elucidated.

Methods

In this study, we examined 22 patients with drug eruptions caused by tribenoside. Patch tests were performed to investigate in vivo cellular reactions. Laboratory investigations were carried out by lymphocyte transformation tests and basophil activation tests.

Results

We found a positive patch test reaction to tribenoside in one patient. The lymphocyte transformation test elicited a borderline positive reaction in one patient, and the basophil activation test gave a clearly positive reaction in another patient.

Conclusion

The diagnosis of drug hypersensitivity reactions is a challenge. Both delayed and immediate immunologic response may play a role in the etiology of tribenoside-induced exanthemas. Our investigation and results indicate that benzoic acid could be the antigenic determinant in drug hypersensitivity to tribenoside.     

Partial‐volume modeling reveals reduced gray matter in specific thalamic nuclei early in the time course of psychosis and chronic schizophrenia

The structural complexity of the thalamus, due to its mixed composition of gray and white matter, make it challenging to disjoint and quantify each tissue contribution to the thalamic anatomy. This work promotes the use of partial‐volume‐based over probabilistic‐based tissue segmentation approaches to better capture thalamic gray matter differences between patients at different stages of psychosis (early and chronic) and healthy controls. The study was performed on a cohort of 23 patients with schizophrenia, 41 with early psychosis and 69 age and sex‐matched healthy subjects. Six tissue segmentation approaches were employed to obtain the gray matter concentration/probability images. The statistical tests were applied at three different anatomical scales: whole thalamus, thalamic subregions and voxel‐wise. The results suggest that the partial volume model estimation of gray matter is more sensitive to detect atrophies within the thalamus of patients with psychosis. However all the methods detected gray matter deficit in the pulvinar, particularly in early stages of psychosis. This study demonstrates also that the gray matter decrease varies nonlinearly with age and between nuclei. While a gray matter loss was found in the pulvinar of patients in both stages of psychosis, reduced gray matter in the mediodorsal was only observed in early psychosis subjects. Finally, our analyses point to alterations in a sub‐region comprising the lateral posterior and ventral posterior nuclei. The obtained results reinforce the hypothesis that thalamic gray matter assessment is more reliable when the tissues segmentation method takes into account the partial volume effect.