p53 and MDM2 expression in odontogenic cysts and tumours

OBJECTIVE: The aim of this report was to assess p53 and MDM2 expression in odontogenic cysts and tumours, as they are known to play important roles in cell proliferation and tumorigenesis. MATERIALS AND METHODS: The expression of p53 and MDM2 proteins was determined immunohistochemically in 51 formalin-fixed, paraffin embedded specimens of odontogenic cysts and tumours.RESULTS: No positivity to p53 was found in the cases studied. MDM2 expression in ameloblastoma was higher than in radicular cysts, but lower than that observed in odontogenic keratocysts. No difference was observed between MDM2 expression in radicular cyst and adenomatoid odontogenic tumour. The clear-cell odontogenic ameloblastoma presented strong immunoreaction to this antigen.CONCLUSIONS: The results suggest that MDM2 overexpression may be involved in the pathogenesis of some odontogenic lesions.     

The transition from fetus to neonate – an endocrine perspective

Gluckman PD, Sizonenko SV, Bassett NS. The transition from fetus to neonate - an endocrine perspective. Acta Pædiatr 1999; Suppl 428: 7–11. Stockholm. ISSN 0803–5326
The transition from fetus to neonate involves three phases: late gestation, parturition and the processes needed to establish independent homoeostatic regulation after separation from the placenta. These phases are regulated by a series of fetal and placental endocrine events. Glucocorticoids have an important role in the preparation for birth, including involvement in lung and cardiac development, and the maturation of enzymes in a variety of pathways. Fetal Cortisol production is, in turn, also under hormonal control. Parturition is a complex process, which is still poorly understood in humans. The final steps are largely dependent on the effect of prostaglandin F_2α on the myometrium associated with increased oxytocin activity. The transition to birth is accompanied by changes in respiration, circulation, glucose homoeostasis, and the onset of independent oral feeding and thermoregulation. Several examples of endocrine components of the transition from fetal to neonatal life are reviewed here: the role of prostanoids, the onset of thermogenesis, and changes in the thyroid hormone and growth hormone axes. The effects of hormone levels on prematurity and growth retardation are also discussed. □ Birth transition, fetus, gestation, hormonal control, neonate, parturition     

Brassiere wearing and breast cancer risk: A systematic review and meta-analysis

AIM: To evaluate existing evidence for the association between different type of brassiere exposures and the risk of breast cancer. METHODS: Ovid Medline, CINAHL, Cochrane Data Base of Systematic Reviews, Pubmed, Scopus, Proquest, Sciencedirect, Wiley Online Library, WanFang Data, Hong Kong Index to Chinese Periodicals, China Journal Net, Chinese Medical Current Contents, Chinese Biomedical Literature Database, China Academic Journals Full-Text database, Taiwan Electronic Periodical Services and HyRead; reference lists of published studies; original research studies published in English or Chinese examining the association between type and duration of brassiere-wearing and breast cancer risk. Data were abstracted by a first reviewer and verified by a second. Study quality was rated according to predefined criteria. “Fair” or “good” quality studies were included. Results were summarised by meta-analysis whenever adequate material was available. RESULTS: Twelve case-control studies were included in the review. Meta-analysis showed brassiere wearing during sleep was associated with a two times of increased odds. CONCLUSION: The present review demonstrates insufficient evidence to establish a positive association between the duration and type of brassiere wearing and breast cancer. Further research is essential; specifically, a large-scale epidemiological study of a better design is needed to examine the association between various forms of brassiere exposure in detail and breast cancer risk, with adequate control of confounding variables.     

The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate

BACKGROUND AND PURPOSE

BAF312 is a next-generation sphingosine 1-phosphate (S1P) receptor modulator, selective for S1P₁ and S1P₅ receptors. S1P₁ receptors are essential for lymphocyte egress from lymph nodes and a drug target in immune-mediated diseases. Here, we have characterized the immunomodulatory potential of BAF312 and the S1P receptor-mediated effects on heart rate using preclinical and human data.

EXPERIMENTAL APPROACH

BAF312 was tested in a rat experimental autoimmune encephalomyelitis (EAE) model. Electrophysiological recordings of G-protein-coupled inwardly rectifying potassium (GIRK) channels were carried out in human atrial myocytes. A Phase I multiple-dose trial studied the pharmacokinetics, pharmacodynamics and safety of BAF312 in 48 healthy subjects.

KEY RESULTS

BAF312 effectively suppressed EAE in rats by internalizing S1P₁ receptors, rendering them insensitive to the egress signal from lymph nodes. In healthy volunteers, BAF312 caused preferential decreases in CD4⁺ T cells, T_naïve, T_{central memory} and B cells within 4–6 h. Cell counts returned to normal ranges within a week after stopping treatment, in line with the elimination half-life of BAF312. Despite sparing S1P₃ receptors (associated with bradycardia in mice), BAF312 induced rapid, transient (day 1 only) bradycardia in humans. BAF312-mediated activation of GIRK channels in human atrial myocytes can fully explain the bradycardia.

CONCLUSION AND IMPLICATIONS

This study illustrates species-specific differences in S1P receptor specificity for first-dose cardiac effects. Based on its profound but rapidly reversible inhibition of lymphocyte trafficking, BAF312 may have potential as a treatment for immune-mediated diseases.     

Ultrasound and Doppler findings in a rare case of Castleman's disease of the parotid

Castleman''s disease of the parotid gland is an extremely rare entity, with fewer than 20 cases reported in world literature so far and only 1 previous case report describing the ultrasound findings. The Doppler findings of parotid Castleman''s disease have never been described before to the best of the authors'' knowledge. This report describes the ultrasonographic and Doppler findings in a histopathologically proven case of Castleman''s disease of the left parotid gland in a young man.     

Platelet-activating factor receptor (PAF-R)-dependent pathways control tumour growth and tumour response to chemotherapy

Background  

Phagocytosis of apoptotic cells by macrophages induces a suppressor phenotype. Previous data from our group suggested that this occurs via Platelet-activating factor receptor (PAF-R)-mediated pathways. In the present study, we investigated the impact of apoptotic cell inoculation or induction by a chemotherapeutic agent (dacarbazine, DTIC) on tumour growth, microenvironmental parameters and survival, and the effect of treatment with a PAF-R antagonist (WEB2170). These studies were performed in murine tumours: Ehrlich Ascitis Tumour (EAT) and B16F10 melanoma.     

Evidence that fibrinogen γ′ directly interferes with protofibril growth: implications for fibrin structure and clot stiffness

Summary. Background: Fibrinogen contains an alternatively spliced γ‐chain (γ′), which mainly exists as a heterodimer with the common γA‐chain (γA/γ′). Fibrinogen γ′ has been reported to inhibit thrombin and modulate fibrin structure, but the underlying mechanisms are unknown. Objective: We aimed to investigate the molecular mechanism underpinning the influence of γ′ on fibrin polymerization, structure and viscoelasticity. Methods: γA/γA and γA/γ′ fibrinogens were separated using anion exchange chromatography. Cross‐linking was controlled with purified FXIIIa and a synthetic inhibitor. Fibrin polymerization was analyzed by turbidity and gel‐point time was measured using a coagulometer. We used atomic force microscopy (AFM) to image protofibril formation while final clot structure was assessed by confocal and scanning electron microscopy. Clot viscoelasticity was measured using a magnetic microrheometer. Results: γA/γ′ fibrin formed shorter oligomers by AFM than γA/γA, which in addition gelled earlier. γA/γ′ clots displayed a non‐homogenous arrangement of thin fibers compared with the uniform arrangements of thick fibers for γA/γA clots. These differences in clot structure were not due to thrombin inhibition as demonstrated in clots made with reptilase. Non‐cross‐linked γA/γA fibrin was approximately 2.7 × stiffer than γA/γ′. Cross‐linking by FXIIIa increased the stiffness of both fibrin variants; however, the difference in stiffness increased to approximately 4.6 × (γA/γA vs. γA/γ′). Conclusions: Fibrinogen γ′ is associated with the formation of mechanically weaker, non‐uniform clots composed of thin fibers. This is caused by direct disruption of protofibril formation by γ′.     

Hemolytic disease of the newborn caused by anti-Rh32 and demonstration that RN encodes rhi (Ce,Rh7)

A family is described in which the mother made anti-Rh32 as a result of pregnancy; her second liveborn child had hemolytic disease of the newborn and required an exchange transfusion. In investigating the family, it was found that the father's RN gene did not make rhi and that his second Rh gene made normal amounts of c and e but a reduced amount of f. In the two children of the couple, who inherited a normal r or Ro from their mother, the paternally derived RN encoded an amount of rhi that could be detected in direct typing tests. In the father, lack of production of rhi by RN may have represented a suppressive effect of the ce(f) gene in trans to RN or the presence of an unlinked suppressor of Rh that might also have been responsible for the reduced production of f by his r or Ro gene. The two children in this family are the first persons in whom RN has been shown to make rhi.