Shared psychotic disorder - a case study of folie à famille.

BACKGROUND: Folie à famille is a rare form of shared psychotic disorder. It is defined as the transfer of delusions from one person to another. CASE REPORT: This paper presents a case of shared psychotic disorder in two brothers, aged 16 and 17 and their mother who were admitted on the same day at the Clinic for psychiatry. The inducer was a mother, suffering from schizophrenia. She transferred her delusions to her sons. Both boys produced mostly the same paranoid delusions, that the others have been recording and monitoring them since their father died. After few days, the older boy, who had more severe psychotic symptoms, was treated with aripiprazole, while both received anxiolytics in low dosage. RESULTS: We observed a withdrawal of psychotic psychopathology in both kids. Genetic burden, social isolation and strong emotional connection of family members are factors that have contributed to the development of shared psychotic disorder in this case. CONCLUSIONS: The new approach of treatment for induced psychosis includes not only separation from the primary case, but also specific pharmacotherapy. It is necessary to think about this clinical entity, because this delusional disorder needs specific treatment, with better prognostic outcomes.

The importance of minimal residual disease for detection of late relapse in Bprecursor acute lymphoblastic leukemia.

BACKGROUND: The minimal residual disease (MRD) level in patients with B-precursor acute lymphoblastic leukemia (B-ALL) is the strongest independent predictor of relapse and survival. Assessment of MRD plays a crucial role in the treatment of B-ALL. CASE REPORT: We performed long-term monitoring of a 30-year-old woman with B-ALL of standard risk for MRD using multiparametric flow cytometry (MFC). After five years of monitoring, molecular relapse of the disease was confirmed. CONCLUSION: This case illustrates that more extended monitoring for MRD, even by only MFC when other newer sophisticated diagnostics are not available, is essential in detecting early relapse in patients with B-ALL of standard risk. HIPPOKRATIA 2022, 26 (1):38-40.

FAMILIAL CIRCUMSTANCES AND PSYCHOLOGICAL CHALLENGES IN ADOLOSCENTS WITH HISTORY OF CHILDHOOD ABUSE.

Violence, child abuse and neglect, which can lead to physical, psychological and social impairment and cause serious long-term consequences, are widespread throughout the world. The aim of our study is to examine the characteristics of the family and the emotional-behavioral difficulties of adolescents who were abused in childhood, compared with those who did not experience abuse. Sixty participants of both genders aged 12 to 18 years were divided into two groups (abused adolescents and the control group). The medical documentation and the self-report questionnaire for youth (SRQY) were used for data collection.The data were analyzed by JASP 0.8.5.1 by ANOVA. 46.67% of adolescents reported that they experienced neglect, 10% physical abuse, 3.33% emotional abuse, and 40% have suffered from several types of abuse. Usually, they are abused by both parents. In abusive families, the average number of siblings, divorced and single parents is higher than in non-abusive families and the level of parents' education is lower compared with the control group.The adolescents with abusive experience have more somatic disturbances, delinquency, and aggressive behavior (p<0.01) than controls.Adolescents with childhood neglect and abuse develop multiple psychopathological difficulties that require psychological and psychiatric intervention to prevent the negative consequences in adulthood.

Proliferative characteristics of Philadelphia-negative myeloproliferative neoplasms - clinical implications.

INTRODUCTION: Philadelphia-negative myeloproliferative neoplasms (Ph- MPN) are characterized by overproduction of one or more blood cell lines. METHODS: We studied the proliferative characteristics of 91 patients with de novo Ph- MPN. Colony-forming cells (CFC) and endogenous colonies (EC), from bone marrow (BM) and/or peripheral blood (PB), were analyzed by colony assay based on methylcellulose. The level of circulating CD34+ cells was determined by flow cytometry. RESULTS: The total number of PB CFC in primary myelofibrosis (PMF) was increased compared to the control sample (P < 0.01) and essential thrombocythemia (ET) (P < 0.05). The highest number of BM and PB EC was observed in polycythemia vera (PV) (P < 0.01). Increased levels of CD34+ cells characterized early-prefibrotic (57%) and advanced-fibrotic PMF (90%) as compared to PV (34%) and ET (32%) (P < 0.01). In the whole Ph- MPN group, the total number of PB CFC (P < 0.01), PB EC (P < 0.05), and CD34+ cells (P < 0.01) correlated with the degree of BM fibrosis. Higher levels of circulating CD34+ cells in PMF correlated with the total number of PB EC (P < 0.05) and degree of BM fibrosis (P < 0.01). CONCLUSIONS: Exploration of the PB proliferative characteristics of Ph- MPN on diagnosis may be helpful in revealing early-prefibrotic PMF. Monitoring the levels of circulating CD34+ cells may provide a sensitive indicator of fibrotic evolution in PV and PMF.

Influence of misdiagnosis on the course of bipolar disorder.

BACKGROUND: It is very common that the diagnosis of bipolar disorder comes with several years of delay. This premise is supported by the fact that this diagnosis is almost always set after longitudinal monitoring of symptoms and by the fact that this disorder is often unrecognized or misdiagnosed. AIM: The aim of this study was to determine the incidence of misdiagnosed bipolar disorder and to explore its influence on the further course of the disorder. PATIENTS AND METHODS: The research was provided as a naturalistic study, which included 65 bipolar patients admitted to the Hospital. We examined medical records of the first episode and five-year follow-up of the course of the disease. The average number of episodes was compared between the group with properly diagnosed first episode and the group with wrongly diagnosed first episode in the observed five-year period. T-test was used in this study, in addition to descriptive parameters, mean, median, standard deviation and coefficient of variation. RESULTS: In the sample over which the survey was conducted 52% of the first episodes of bipolar disorder were wrongly diagnosed. We found a statistically significant difference (t = 1.84; p < 0.05) in the number of episodes that followed the first episode between patients whose first episode was appropriately diagnosed and patients whose first episode has not been properly diagnosed. CONCLUSIONS: There is a high number of unrecognized and misdiagnosed bipolar disorders. Inadequate diagnosis leads to inadequate treatment of the disorder. Number of next episodes in period of follow up is statistically significantly connected with the adequacy of diagnose.

Gene discovery in oral squamous cell carcinoma through the Head and Neck Cancer Genome Anatomy Project: confirmation by microarray analysis.

The near completion of the human genome project and the recent development of novel, highly sensitive high-throughput techniques have now afforded the unique opportunity to perform a comprehensive molecular characterization of normal, precancerous, and malignant cells, including those derived from squamous carcinomas of the head and neck (HNSCC). As part of these efforts, representative cDNA libraries from patient sets, comprising of normal and malignant squamous epithelium, were generated and contributed to the Head and Neck Cancer Genome Anatomy Project (HN-CGAP). Initial analysis of the sequence information indicated the existence of many novel genes in these libraries [Oral Oncol 36 (2000) 474]. In this study, we surveyed the available sequence information using bioinformatic tools and identified a number of known genes that were differentially expressed in normal and malignant epithelium. Furthermore, this effort resulted in the identification of 168 novel genes. Comparison of these clones to the human genome identified clusters in loci that were not previously recognized as being altered in HNSCC. To begin addressing which of these novel genes are frequently expressed in HNSCC, their DNA was used to construct an oral-cancer-specific microarray, which was used to hybridize alpha-(33)P dCTP labeled cDNA derived from five HNSCC patient sets. Initial assessment demonstrated 10 clones to be highly expressed (>2-fold) in the normal squamous epithelium, while 14 were highly represented in the malignant counterpart, in three of the five patient sets, thus suggesting that a subset of these newly discovered transcripts might be highly expressed in this tumor type. These efforts, together with other multi-institutional genomic and proteomic initiatives are expected to contribute to the complete understanding of the molecular pathogenesis of HNSCCs, thus helping to identify new markers for the early detection of preneoplastic lesions and novel targets for pharmacological intervention in this disease.

Isotonic biaxial loading of fibroblast-populated collagen gels: a versatile, low-cost system for the study of mechanobiology.

We developed a simple, versatile system for applying a range of biaxial loads to cell-matrix constructs for the study of mechanobiology. The system consists of porous polyethylene bars that are polymerized into a square fibroblast-populated gel and loaded by freely hanging weights attached to sutures routed through a custom loading rig. The cost to manufacture each mold/loading rig pair was less than US dollars 250 and the expected life of the components is up to 10 years. Neonatal and adult cardiac fibroblasts contracted gels to a decreasing extent as external load was increased ( P=0.003) and achieved contraction forces of up to 1.4 mN per million cells. Strain distributions were reasonably homogeneous in the central region of the gel (25% of gel area), but clearly nonhomogeneous outside that central region. The primary advantages of this system are simplicity, low cost, biaxial loading, and the ability to test for a dose-response effect of mechanical load. The current disadvantages are the inability to apply cycling loading and the inhomogeneities introduced by the use of rigid loading bars.

Proteomic profiling of the cancer microenvironment by antibody arrays.

Critical changes in protein expression that enable tumors to initiate and progress originate in the local tissue microenvironment, and there are increasing indications that these microenvironmental alterations in protein expression play critical roles in shaping and directing this process. As a model to better understand how patterns of protein expression shape the tissue microenvironment, we analyzed protein expression in tissue derived from squamous cell carcinoma of the oral cavity through an antibody microarray approach for high-throughput proteomic analysis. Utilizing laser capture microdissection to procure total protein from specific microscopic cellular populations, we demonstrate that quantitative, and potentially qualitative, differences in expression patterns of multiple proteins within epithelial cells reproducibly correlate with oral cavity tumor progression. Furthermore, differential expression of multiple proteins was also found in stromal cells surrounding and adjacent to regions of diseased epithelium that directly correlated with tumor progression of the epithelium. Most of the proteins identified in both cell types are involved in signal transduction pathways, thus we hypothesize that extensive molecular communication involving complex cellular signaling between epithelium and stroma play a key role in driving oral cavity cancer progression.

Activation of epiblast gene expression by the hypoblast layer in the prestreak chick embryo.

Axis formation is a highly regulated process in vertebrate embryos. In mammals, inductive interactions between an extra-embryonic layer, the visceral endoderm, and the embryonic layer before gastrulation are critical both for anterior neural patterning and normal primitive streak formation. The role(s) of the equivalent extra-embryonic endodermal layer in the chick, the hypoblast, is still less clear, and dramatic effects of hypoblast on embryonic gene expression have yet to be demonstrated. We present evidence that two genes later associated with the gastrula organizer (Gnot-1 and Gnot-2) are induced by hypoblast signals in prestreak embryos. The significance of this induction by hypoblast is discussed in terms of possible hypoblast functions and the regulation of axis formation in the early embryo. Several factors known to be expressed in hypoblast, and retinoic acid, synergistically induce Gnot-1 and Gnot-2 expression in blastoderm cell culture. The presence of retinoic acid in prestreak embryos has not yet been directly demonstrated, but exogenous retinoic acid appears to mimic the effects of hypoblast rotation on primitive streak extension, raising the possibility that retinoid signaling plays some role in the pregastrula embryo.

[Effect of vitamin E on erythrocyte enzymes and total antioxidant status in diabetic patients with ischemic heart disease]. / Dejstvo vitamina E na enzime eritrocita i ukupni antioksidantni status kod dijabeticnih bolesnika s ishemijskom bolescu srca.

Lipid peroxidation is thought to be one of the major factors involved in atherogenesis. There is an increasing evidence is increasing that oxidation of LDL cholesterol may be instrumental in atherogenesis. Diabetics are known to be at increased risk of cardiovascular diseases, a phenomenon which has previously been linked to the lipid peroxidation process. As a result, a number of studies have been undertaken to evaluate the effects of antioxidant vitamins on coronary heart disease and risks factors of ischaemic heart disease such as diabetes mellitus. Lipid peroxidation and antioxidant status were studied in 51 patients with ischaemic heart disease and some of with having diabetes mellitus (18%). Results were compared before and after supplementation of 450 mg of tocopherol acetate for three months. SOD were found to be elevated in patients with diabetes and in whole groups of patients after supplementation of tocopherol acetate. Also, TAS was found to be elevated in a subgroup of patients without diabetes and no significant changes were found in glutathion-peroxidase after supplementation. We found statistically significantly decreased mean values of glucose after supplementation in all groups of patients. The monitoring of antioxidant parameters in diabetic patients could be of vital importance in the study of the disease.

Do 5'Hoxd genes play a role in initiating or maintaining A-P polarizing signals in the limb?

The analysis of multiple null mutants generated through targeted disruption indicates that the 5' members of the Hoxd and Hoxa clusters determine the skeletal pattern in the limb by regulating the formation and growth of the different chondrogenic precursors for the skeletal elements. While these studies have established that together these genes are the major players in regulating formation of the limb skeleton, the roles of individual members have often been difficult to evaluate fully due to extensive functional overlap between various 5'Hoxd and 5'Hoxa genes. The analysis of gain-of-function mutants provides a complementary approach to elucidate gene function in the presence of multiple redundancies. This approach has recently revealed that Hoxd-12 can induce Sonic hedgehog and suggests a new role for certain 5'Hoxd genes in the initiation of Sonic hedgehog expression and its maintenance through feedback regulation. Thus, some 5'Hoxd genes may be a part of the regulatory network that positions and reinforces polarizing signals in the posterior-distal limb bud.

Continuing organizer function during chick tail development.

Development of the posterior body (lumbosacral region and tail) in vertebrates is delayed relative to gastrulation. In amniotes, it proceeds with the replacement of the regressed node and primitive streak by a caudal blastema-like mass of mesenchyme known as the tail bud. Despite apparent morphological dissimilarities, recent results suggest that tail development in amniotes is in essence a continuation of gastrulation, as is the case in Xenopus. However, this has been inferred primarily from the outcome of fate mapping studies demonstrating discrete, regionalized cell populations in the tail bud, like those present at gastrulation. Our analysis of the tail bud distribution of several molecular markers that are expressed in specific spatial domains during chick gastrulation confirms these results. Furthermore, we present evidence that gastrulation-like ingression movements from the surface continue in the early chick tail bud and that the established tail bud retains organizer activity. This 'tail organizer' has the expected properties of being able to recruit uncommitted host cells into a new embryonic axis and induce host neural tissue with posteriorly regionalized gene expression when grafted to competent host cells that are otherwise destined to form only extra-embryonic tissue. Together, these results indicate that chick tail development is mechanistically continuous with gastrulation and that the developing tail in chick may serve as a useful experimental adjunct to investigate the molecular basis of inductive interactions operating during gastrulation, considering that residual tail organizing activity is still present at a surprisingly late stage.

Hoxd-12 differentially affects preaxial and postaxial chondrogenic branches in the limb and regulates Sonic hedgehog in a positive feedback loop.

Several 5' members of the Hoxd cluster are expressed in nested posterior-distal domains of the limb bud suggesting a role in regulating anteroposterior pattern of skeletal elements. While loss-of-function mutants have demonstrated a regulatory role for these genes in the developing limb, extensive functional overlaps between various different Hox genes has hampered elucidation of the roles played by individual members. In particular, the function of Hoxd-12 in the limb remains obscure. Using a gain-of-function approach, we find that Hoxd-12 misexpression in transgenic mice produces apparent transformations of anterior digits to posterior morphology and digit duplications, while associated tibial hemimelia and other changes indicate that formation/growth of certain skeletal elements is selectively inhibited. If the digital arch represents an anterior bending of the main limb axis, then the results are all reconcilable with a model in which Hoxd-12 promotes formation of postaxial chondrogenic condensations branching from this main axis (including the anteriormost digit) and selectively antagonizes formation of 'true' preaxial condensations that branch from this main axis (such as the tibia). Hoxd-12 misexpression can also induce ectopic Sonic hedgehog (Shh) expression, resulting in mirror-image polydactyly in the limb. Misexpression of Hoxd-12 in other lateral plate derivatives (sternum, pelvis) likewise phenocopies several luxoid/luxate class mouse mutants that all share ectopic Shh signalling. This suggests that feedback activation of Shh expression may be a major function of Hoxd-12. Hoxd-12 can bind to and transactivate the Shh promoter in vitro. Furthermore, expression of either exogenous Hoxd-11 or Hoxd-12 in cultured limb bud cells, together with FGF, induces expression of the endogenous Shh gene. Together these results suggest that certain 5' Hoxd genes directly amplify the posterior Shh polarizing signal in a reinforcing positive feedback loop during limb bud outgrowth.

Two novel chick T-box genes related to mouse Brachyury are expressed in different, non-overlapping mesodermal domains during gastrulation.

The mouse Brachyury (T) gene plays critical roles in the genesis of normal mesoderm during gastrulation and in the maintenance of a functioning notochord. Abrogation of Brachyury (T) expression within the chordamesoderm of homozygous null mutants nevertheless spares anterior axis formation. An intriguing possibility to explain the preservation of anterior axis formation in these mutants would be the existence of other genes compensating for the loss of Brachyury. This compensation and the recent demonstration that Brachyury is the prototype for an evolutionarily conserved family, prompted a search for other T-box genes participating in axis formation. The chick Brachyury orthologue and two related chick T-box genes that are expressed at the onset of gastrulation have been isolated. One of these novel genes (Ch-TbxT) becomes restricted to the axial mesoderm lineage and is a potential candidate for complementing or extending Brachyury function in the anterior axis (formation of the head process, prechordal plate). The other gene (Ch-Tbx6L), together with chick T, appears to mark primitive streak progenitors before gastrulation. As cells leave the primitive streak, Ch-Tbx6L becomes restricted to the early paraxial mesoderm lineage and could play a role in regulating somitogenesis.

Differentiation potential of rat amnion.

The differentiation potential of rat amnion was investigated by explantation to different extrauterine sites and by culturing in vitro. Amnion differentiated into full skin by a process that is morphologically indistinguishable from normal skin development (interactions of the surface embryonic ectoderm and underlying mesenchyme). This process is not dependent on the age of the amnion but is dependent on the culture conditions used. Possible implications of these findings are discussed.

The organizer-associated chick homeobox gene, Gnot1, is expressed before gastrulation and regulated synergistically by activin and retinoic acid.

Gnot1, a Not (for notochord) family homeobox gene, is expressed in the chick pregastrulation blastoderm. Gnot1 expression in the epiblast is upregulated as the posteriorly derived hypoblast moves forward anteriorly to form a layer beneath it, which is of particular interest considering the known inductive role of the hypoblast in axis formation in the chick. Both activin and retinoic acid are able to activate Gnot1 expression in cultured blastodermal cells and show a strong synergistic effect when applied in combination. Strong superinduction of Gnot1 transcripts in the presence of cycloheximide also indicates the presence of a potent and labile intracellular inhibitor capable of modulating Gnot1 expression. During gastrulation, Gnot1 transcripts become localized specifically to tissues associated with "organizer" function (Hensen's node, head process, notochord). The expression data and the response to mesoderm inducing factors and axial "caudalizing" signals suggest that Gnot1 may be involved in specification of the embryonic body axis and could play a part in regulating features of the trunk/tail organizer in the chick embryo.

Expression of TGF-beta s and their receptors during implantation and organogenesis of the mouse embryo.

The spatial and temporal expression of the transforming growth factor beta (TGF-beta) receptors type III, type II, and two types I (ALK-5 and Tsk 7L) and their ligands TGF-beta 1 and TGF-beta 2 in postimplantation mouse development were examined using the reverse transcription polymerase chain reaction (RT-PCR), in situ hybridization, and immunohistochemistry. With RT-PCR, expression of the signaling TGF-beta receptors (types II and ALK-5) was shown to be absent in isolated germ layers of 6.0-7.5 days postcoitum (dpc) embryos, whereas the type III receptor and Tsk 7L were differentially expressed at these stages. In contrast, all TGF-beta receptor types were expressed at these stages in the pregnant uterus and decidua. TGF-beta 1 and TGF-beta 2 transcripts were detected before gastrulation at 6.5 dpc only in the visceral embryonic endoderm, whereas during gastrulation, at 7.5 dpc TGF-beta 1 and TGF-beta 2 mRNA was detected in all three germ layers. In situ hybridization and immunohistochemistry of the expression of the TGF-beta type II receptor confirmed the data obtained by RT-PCR. Furthermore, the type II receptor was detected in the extraembryonic ectoderm of 7.5 dpc embryos. In the embryo proper, TGF-beta type II receptor expression was detected only later in differentiating tissues and developing organs, but not in the brain and neural tube. Since the expression of the type II receptor may essentially determine whether a cell is able to respond to TGF-beta, the results are consistent with the view that TGF-beta s might be implicated in embryo implantation and organogenesis, but are not involved in gastrulation of the embryo.

p185neu is expressed in yolk sac during rat postimplantation development.

We have shown that the neu oncogene product (p185neu) is not present in the rat embryo before organogenesis. However, coincident with the onset of organogenesis, p185neu was detected in neural and connective tissue as well as in the secretory epithelium as was described by Kokai et al. (1987). In addition, p185neu is also expressed in the rat visceral yolk sac (VYS) endodermal cells but not in the mesenchymal and mesothelial layers of the same structure nor in the amnion. The first detectable sign of p185neu expression in VYS was found at d 11 of gestation and the levels of protein increased towards the end of pregnancy. In the yolk sac carcinoma (YSC), which is considered to be the malignant counterpart of the rat yolk sac, p185neu was observed only within columnar epithelial cells (the visceral component of the neoplasm) while parietal endoderm-like cells were devoid of detectable protein. From d 9 of pregnancy up to delivery some of the trophoblastic giant cells also showed a faint to moderate immunoreactivity. Results are presented which would indicate a possible role of p185neu in rat embryogenesis.

Development of separated germ layers of rodent embryos on ectopic sites: a reappraisal.

The method of separation of germ layers of rodent embryos by treating the embryonic shields with proteolytic enzymes and by microsurgery with the subsequent transplantation to ectopic sites has helped to gain a more detailed insight into what is going on during gastrulation in mammals. The space under the kidney capsule of adult animals seems to be the most appropriate ectopic site for transplantation of early postimplantation rat embryos or separated germ layers. After transplantation the grafts develop into teratomas whose complex histological structure reflects the initial developmental capacities of the graft. At the pre-primitive streak and the early primitive streak stages the primitive ectoderm differentiates into tissue derivatives of all three definitive germ layers, often in complex organotypic combinations. This is indirect evidence that all cells of the embryonic body originate from the primitive embryonic ectoderm. Halves of the primitive ectoderm obtained by a longitudinal or transverse cut through the egg cylinder give the same result. At the head fold stage the capacity for differentiation of the ectoderm is restricted to ectodermal and mesodermal derivatives. One day before gastrulation the isolated primitive ectoderm is not able to differentiate as renal isograft. The mesoderm isolated at the head fold stage and at later stages when its segmentation occurs, differentiates almost exclusively into the brown adipose tissue. The embryonic endoderm differentiates only in combination with the mesoderm. After transplantation the embryonic ectoderm loses its epithelial organization and breaks up into a mass of mesenchyme-like cells in which epithelial structures subsequently appear and differentiate in a way reminiscent of the reaggregation of cells in mixed cell suspension in vitro.