Family patterns of developmental dyslexia: Clinical findings

Two separate groups of dyslexia families were ascertained through probands attending special schools for dyslexic students. An additional control group of families was ascertained through randomly selected students attending public schools. The 3 groups were interviewed by questionnaire about the family's demographic characteristics, and about the incidence of reading and spelling disorders in all first and second order relatives. One group of dyslexia families was also examined by standardized intelligence and academic achievement tests. Developmental dyslexia was found to aggregate in families; there were 4–5 times as many affected males as females among clinically identified students attending the special schools, but the sex ratio of affected relatives after probands had been excluded was approximately 1.4 males for every female. Sibs were at greater risk for reading difficulties when one parent was affected than when neither parent was affected. Sibs were also at greater risk for academic difficulties, and affected sibs were more severely impaired, when the father rather than the mother was the affected parent. In dyslexia families with 2 affected parents, the sibs were at greater risk, and the affected sibs were more severely impaired, than in families where only one parent was affected. Moreover, in families with 2 affected parents, both of the parents were more severely impaired in reading and spelling than parents of the same sex in families with one affected parent. Some indirect evidence is presented that assortative mating may codetermine patterns of affectedness in dyslexia families. © 1994 Wiley-Liss, Inc.     

Relationship between beta‐herpesviruses reactivation and development of complications after autologous peripheral blood stem cell transplantation

The relationship between beta‐herpesviruses reactivation and the development of complications after autologous peripheral blood stem cell transplantation was investigated. Viral genomic sequences were detected by the polymerase chain reaction, virus‐specific antibodies by ELISA, and human herpesvirus (HHV)‐6 variants by restriction endonuclease analysis. Virus reactivation, serum levels of tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6, soluble IL‐2 receptor (sIL‐2R), IL‐2, and IL‐4 were compared with clinical features in 44 patients before and after transplantation. Anti‐CMV and anti‐HHV‐6 antibodies were found in 70.5% and 81.8% of patients, respectively. The frequency of plasma viremia was significantly higher in patients after transplantation (41% vs. 11.4%). Reactivation of more than one virus was identified in 55.6% of patients and reactivation of HHV‐7 alone in 44.4%. In cases of concurrent infection, HHV‐7 was reactivated before HHV‐6, and both HHV‐6 and HHV‐7 were reactivated before CMV. There was a significant increase in HHV‐6 load in peripheral blood leukocytes DNA during viremia. In all cases HHV‐6B variant was detected. Complications after transplantation occurred in 27.3% of patients and virus reactivation was detected in all patients with complications. The significant increases in the rate of HHV‐6 and HHV‐7 reactivation and in serum levels of TNF‐α, IL‐1β, and sIL‐2R, as well as aggravated immunosuppression, suggest that both viruses were involved in the complications after autologous peripheral blood stem cell transplantation, via their immunomodulatory activity. The kinetics of reactivation suggests a potential role of HHV‐7 as a co‐factor of HHV‐6 reactivation, and of both HHV‐6 and HHV‐7 as co‐factors of CMV reactivation. J. Med. Virol. 84:1953–1960, 2012. © 2012 Wiley Periodicals, Inc.     

Lentiviral shRNA silencing of murine bone marrow cell CCR2 leads to persistent knockdown of CCR2 function in vivo

A major barrier in hematopoietic gene function studies is posed by the laborious and time-consuming generation of knockout mice with an appropriate genetic background. Here we present a novel lentivirus-based strategy for the in situ generation of hematopoietic knockdowns. A short hairpin RNA (shRNA) was designed targeting murine CC-chemokine receptor 2 (CCR2), which was able to specifically blunt CCR2 expression at the mRNA, protein, and functional levels in vitro. Reconstitution of irradiated recipient mice with autologous bone marrow that had been ex vivo transduced with shRNA lentivirus led to persistent down-regulation of CCR2 expression, which translated into a 70% reduction in CCR2-dependent recruitment of macrophages to an inflamed peritoneal cavity without noticeable side effects on related chemokine receptors or general inflammation status. These findings clearly demonstrate the potential of shRNA lentivirus-infected bone marrow transplantation as a rapid and effective method to generate hematopoietic knockdowns for leukocyte gene function studies.     

Practices and perceptions on intrauterine contraception among Latvian obstetrician-gynecologists

BACKGROUND: To investigate the professional activity and perceptions of intrauterine contraception among Latvian obstetrician-gynecologists. METHODS: A questionnaire was completed by 122 Latvian obstetrician-gynecologists attending an annual meeting. Statistical analysis was done with the Epi-Info 2002 statistical package. RESULTS: Every day contraceptive consulting was done by 91.8% of physicians and 98.4% reported ever having inserted intrauterine contraception. The majority of doctors reported careful selection of intrauterine contraception candidates, including screening for sexually transmitted infections before insertion. Intrauterine contraception insertion was definitely excluded in women without a stable monogamous relationship only by 9.8%. A causal relationship between intrauterine contraception and pelvic inflammatory disease was believed by 52.5%. Many doctors sometimes prescribed prophylactic antibiotics before or immediately after intrauterine contraception insertion. However, antibiotics were never prescribed before intrauterine contraception insertion by 50.8%. Younger doctors had significantly more often themselves used combined oral contraceptives than had older doctors, whereas older doctors more often had been intrauterine contraception users. Of current and former intrauterine contraception users, 93.4% were satisfied with this contraceptive method. CONCLUSIONS: Latvian obstetrician-gynecologists have wide experience in contraception counseling of intrauterine contraception, but some gaps in the theoretical knowledge of doctors about intrauterine contraception were identified. We could not find any significant differences in attitudes to and personal experience with contraceptive methods between older and younger generations, nor were there any differences between genders of obstetrician-gynecologists.     

Interaction of Muc2 and Apc on Wnt signaling and in intestinal tumorigenesis: potential role of chronic inflammation

Somatic mutations of the adenomatous polyposis coli (APC) gene are initiating events in the majority of sporadic colon cancers. A common characteristic of such tumors is reduction in the number of goblet cells that produce the mucin MUC2, the principal component of intestinal mucus. Consistent with these observations, we showed that Muc2 deficiency results in the spontaneous development of tumors along the entire gastrointestinal tract, independently of deregulated Wnt signaling. To dissect the complex interaction between Muc2 and Apc in intestinal tumorigenesis and to elucidate the mechanisms of tumor formation in Muc2(-/-) mice, we crossed the Muc2(-/-) mouse with two mouse models, Apc(1638N/+) and Apc(Min/+), each of which carries an inactivated Apc allele. The introduction of mutant Muc2 into Apc(1638N/+) and Apc(Min/+) mice greatly increased transformation induced by the Apc mutation and significantly shifted tumor development toward the colon as a function of Muc2 gene dosage. Furthermore, we showed that in compound double mutant mice, deregulation of Wnt signaling was the dominant mechanism of tumor formation. The increased tumor burden in the distal colon of Muc2/Apc double mutant mice was similar to the phenotype observed in Apc(Min/+) mice that are challenged to mount an inflammatory response, and consistent with this, gene expression profiles of epithelial cells from flat mucosa of Muc2-deficient mice suggested that Muc2 deficiency was associated with low levels of subclinical chronic inflammation. We hypothesize that Muc2(-/-) tumors develop through an inflammation-related pathway that is distinct from and can complement mechanisms of tumorigenesis in Apc(+/-) mice.     

Population screening for hereditary and familial cancer syndromes in Valka district of Latvia

Background

The growing possibilities of cancer prevention and treatment as well as the increasing knowledge about hereditary cancers require proper identification of the persons at risk. The aim of this study was to test the outcome of population screening in the scientific and practical evaluation of hereditary cancer.

Methods

Population screening for hereditary cancer was carried out retrospectively in a geographic area of Latvia. Family cancer histories were collected from 18642 adults representing 76.6% of the population of this area. Hereditary cancer syndromes were diagnosed clinically. Molecular testing for BRCA1 founder mutations 300 T/G, 4153delA and 5382insC was conducted in 588 persons who reported at least one case of breast or ovary cancer among blood relatives.

Results

Clinically, 74 (0.40%; 95% confidence interval (CI): 0.32 - 0.50%) high-risk and 548 (2.94%, 95% CI: 2.71 - 3.19) moderate-risk hereditary cancer syndromes were detected covering wide cancer spectrum. All syndromes were characterised by high cancer frequency among blood relatives ranging 8.6 - 46.2% in contrast to spouse correlation of 2.5 - 3.6%. The mean age of cancer onset ranged 38.0 - 72.0 years in different syndromes. The BRCA1 gene mutations were identified in 10 (1.7%; 95% CI: 0.9 - 3.1%) probands. Families with established BRCA1 gene founder mutations were identified with the frequency 1:2663 clinically screened persons.

Conclusions

Population screening is a useful practical tool for the identification of persons belonging to families with high frequency of malignant tumours. The whole hereditary and familial cancer spectrum along with the age structure was identified adjusting follow-up guidelines. Another benefit of the population screening is the possibility to identify oncologically healthy persons belonging to hereditary and familial cancer families so that appropriate surveillance can be offered. Clinical diagnostics is appropriate for population screening purposes; molecular investigation provides additional information. In collaboration with family doctors, the screening is technically manageable as characterised by high compliance.     

Family patterns of developmental dyslexia,part II: Behavioral phenotypes

The motor control of bimanual coordination and motor speech was compared between first degree relatives from families with at least 2 dyslexic family members, and families where probands were the only affected family members. Half of affected relatives had motor coordination deficits; and they came from families in which probands also showed impaired motor coordination. By contrast, affected relatives without motor deficits came from dyslexia families where probands did not have motor deficits. Motor coordination deficits were more common and more severe among affected offspring in families where both parents were affected than among affected offspring in families where only one parent was affected. However, motor coordination deficits were also more common and more severe in affected parents when both parents were affected than among affected parents in families where only one parent was affected. We conclude that impaired temporal resolution in motor action identifies a behavioral phenotype in some subtypes of developmental dyslexia. The observed pattern of transmission for motor deficits and reading impairment in about half of dyslexia families was most congruent with a genetic model of dyslexia in which 2 codominant major genes cosegregate in dyslexia pedigrees where the proband is also motorically impaired. © 1995 Wiley-Liss, Inc.