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PubMed2004

Acute and chronic graft-versus-host disease after ablative and nonmyeloablative conditioning for allogeneic hematopoietic transplantation.

In this study, we evaluated the influence of nonmyeloablative and ablative conditioning regimens on the occurrence of acute and chronic graft-versus-host disease (GVHD). One hundred thirty-seven patients undergoing matched-related sibling transplantations received the same GVHD prophylaxis. Myeloablative regimens included intravenous busulfan/cyclophosphamide (n=45) and fludarabine/melphalan (n=29). Patients in the nonmyeloablative group (n=63) received fludarabine/idarubicin/cytarabine, cisplatin/fludarabine/idarubicin, and fludarabine/cyclophosphamide. The actuarial rate of grade II to IV acute GVHD was significantly higher (hazard ratio, 3.6; 95% confidence interval, 1.5-8.8) in patients receiving ablative regimens (36%) compared with the nonmyeloablative group (12%). The cumulative incidence of chronic GVHD was higher in the ablative group (40%) compared with the nonmyeloablative group (14%). The rates were comparable within the first 200 days and were significantly higher in the ablative group beyond day 200 (hazard ratio, 5.2; 95% confidence interval, 1.2-23.2). Nonrelapse and GVHD-related mortality were relatively low in both groups. The use of the described nonmyeloablative preparative regimens was associated with a reduced incidence of grade II to IV acute GVHD and chronic GVHD compared with the busulfan/cyclophosphamide and fludarabine/melphalan transplant regimens. It is interesting to note that nonrelapse mortality with nonmyeloablative regimens in older and more debilitated patients was low (14%) and comparable to that achieved with standard high-dose regimens in younger patients.

Acute Disease↗
PubMed2005

Homozygosity for premature stop codon of the MHC class I chain-related gene A (MIC-A) is associated with early activation of islet autoimmunity of DR3/4-DQ2/8 high risk DAISY relatives.

We hypothesized that homozygosity for the major histocompatibility complex (MHC) class I chain-related gene A (MIC-A)5.1 allele with premature stop codon would increase diabetes risk of individuals followed from infancy in the DAISY study (Diabetes Autoimmunity Study in the young). Forty five percent (10/22) of relatives (siblings and offspring cohort, SOC) who developed anti-islet autoantibodies were MIC-A5.1/5.1 homozygous. Of SOC individuals without autoantibodies, 12/58 (19%, p = 0.02) were MIC-A5.1 homozygous. By life table analysis of expression of autoantibodies, DR3-DQ2/ DR4-DQ8 more than 50% of MIC-A5.1 homozygous children became autoantibody positive by 7 years of age, compared to delayed development of autoantibodies for non-MIC-A5.1/5.1 DR3-DQ2/ DR4-DQ8 children (p = 0.005). For DR3-DQ2/DR4-DQ8 nonrelatives, the risk of activating anti-islet autoimmunity remained low even with MIC-A5.1 homozygosity suggesting that there are additional factors contributing to the marked risk of relatives compared to the general population with the DR3-DQ2/DR4-DQ8 genotype.

Adolescent↗
PubMed1994

Granulocyte colony-stimulating factor after allogeneic bone marrow transplantation.

Hematopoietic growth factors have been shown to be effective in reducing the period of neutropenia after autologous bone marrow transplantation (BMT). Initial concerns over potential aggravation of graft-versus-host disease (GVHD) and increase in the incidence of relapse in patients with myeloid leukemias influenced the number of studies using hematopoietic growth factors after allogeneic BMT. We report the experience with 50 patients treated at a single institution using granulocyte colony-stimulating factor (G-CSF) after allogeneic sibling (n = 30) and matched unrelated (n = 20) BMT. The time to an absolute neutrophil count > or = 500/microL was significantly faster in patients who received G-CSF and cyclosporine and prednisone for GVHD prophylaxis when compared with historical control patients receiving the same GVHD prophylaxis (10 v 13 days, P < .01). A similar accelerated myeloid engraftment was observed for those patients who received the addition of methotrexate for GVHD prophylaxis when compared with historical control patients receiving the same GVHD prophylaxis regimen (16 v 19 days, P < .05). The median time to engraftment for patients receiving a matched unrelated BMT and G-CSF was 17 days (range 13 to 26). We did not observe any increase in GVHD or early mortality in the matched related sibling BMT. The incidence of acute GVHD in the matched unrelated BMT recipients was also low at 21%; however, 9 patients (45%) died within 100 days of the date of BMT, similar to the experience reported with granulocyte-macrophage CSF. This study confirms the efficacy of G-CSF in accelerating myeloid engraftment after allogeneic matched sibling BMT. The higher early mortality associated with patients receiving matched unrelated BMT suggests that randomized controlled trials using G-CSF after allogeneic BMT should be performed.

Adolescent↗
PubMed1984

Genetic basis of male sterility in hybrids between two closely related species of Drosophila.

Drosophila simulans and Drosophila mauritiana are closely related sibling species, the former cosmopolitan and the latter restricted to the small oceanic island of Mauritius. Genetic analysis of male sterility in hybrids between these species shows that at least five loci (one on each chromosome arm) are responsible for this reproductive isolation. This is the most loci that could have been detected with the techniques used and implies that the true genetic divergence for sterility is even greater. The effects of chromosome segments on the character are roughly additive, with the X-linked segment making the largest contribution to sterility. The large effect of X chromosomes on male-limited reproductive isolation and the frequent limitation of hybrid sterility to males may be attributable to fertility interactions between X and Y chromosomes. These results parallel what has been found in other Drosophila species and relate to recent theories of how reproductive isolation evolves in small founder populations.

Animals↗
PubMed1999

Assumptive world of traumatized South African adults.

One way of understanding the impact of traumatic events is through exploration of cognitive changes that confront a traumatized individual. The author investigated changes in individuals' basic assumptions after traumatic experiences. The participants were 65 people who had been traumatized by representatives of the South African apartheid government. From the total sample, 36 participants had witnessed the violent death of a close relative (sibling, mother, or father). The remaining 29 had been tortured and detained. The author administered the World Assumption Scale (R. Janoff-Bulman, 1989), a semistructured questionnaire on basic assumptions developed for the present study, and the Post-Traumatic Stress Disorder Clinical Checklist (American Psychiatric Association, 1994). Traumatic events affected the participants' basic assumptions about the meaning and benevolence of the world. The tortured and detained group and the bereaved group showed differences in their assumptions of self-worth following the trauma. Cognitive approaches can yield invaluable therapeutic insights into strategies for coping with trauma.

Adult↗
PubMed2000

Familial Aggregation and Segregation Analysis of Snoring and Symptoms of Obstructive Sleep Apnea.

To investigate possible modes of inheritance that would explain familial aggregation in obstructive sleep apnea (OSA), familial correlation and segregation analyses were performed on data derived from 584 pedigrees with 2019 cases enrolled in the Tucson Epidemiologic Study of Obstructive Airways Disease (TESOAD) who were at least 10 years of age and who had information pertaining to snoring and daytime sleepiness. Data were obtained from the 9th (May 1984 to October 1985) and 12th (February 1990 to October 1992) surveys of the TESOAD, which is a random, stratified sample of the non-Hispanic Caucasian population of Tucson, Arizona. A snoring phenotype was considered present if it occurred on at least some nights. A "sleep apnea" phenotype was constructed if participants snored and experienced daytime sleepiness. Familial correlations for snoring showed significant mother-child and sibling correlations but not father-child correlations. For sleep apnea, significant parent-daughter but not parent-son or sibling correlations were observed. Segregation analyses for snoring with regressive familial effects and sibling, age, and obesity covariates showed no evidence for mendelian transmission. However, additional familial effects were present that suggested phenotype aggregation from polygenic or environmental factors, or both. For the sleep apnea phenotype, similar segregation analyses indicated that mendelian dominant or codominant models were possible. However, the analyses also suggested that a nongenetic model fit the data as well. In addition, consistent with the familial correlations, specific maternal- and sibling-related effects remained even after inclusion of age, gender, and obesity covariates. These data support the concept that inheritable or shared environmental factors contribute to the development of OSA and that maternal components may be more important than paternal ones.

Journal Article↗
PubMed2004

Attitudes and psychosocial adjustment of unaffected siblings of patients with phenylketonuria.

Sibling illness may contribute to an increased risk of adjustment problems in healthy siblings. Previous studies have reported a variety of effects on healthy individuals who have an ill sibling, but the psychosocial effects of treatable inherited disease on healthy siblings have not yet been investigated. We report the results of a survey study conducted in families with both unaffected and affected children with classic phenylketonuria (PKU), an inherited inborn error of metabolism. The survey included a knowledge test about PKU, and four previously validated instruments designed to assess psychosocial adjustment of unaffected siblings compared to age and sex matched norms. The responses revealed that unaffected adolescent and adult siblings had gaps in their knowledge about the genetic basis of PKU, and had evidence for the presence of adverse psychosocial sequelae. These findings suggest a role for genetic services providers, including genetic counselors, in assisting all members of a family adjust, when the diagnosis of an inborn error of metabolism has been made.

Adaptation, Psychological↗
PubMed2006

Maternal and littermate deprivation disrupts maternal behavior and social-learning of food preference in adulthood: tactile stimulation, nest odor, and social rearing prevent these effects.

Maternal and littermate (social) separation, through artificial rearing (AR), disrupts the development of subsequent maternal behavior and social learning in rats. The addition of maternal-licking-like stimulation during AR, partially reverses some of these effects. However, little is know about the role of social stimuli from littermates and nest odors during the preweaning period, in the development of the adult maternal behavior and social learning. The purpose of this study was to examine the effects of peer- and peer-and-odor rearing on the development of maternal behavior and social learning in rats. Female pups were reared with mothers (mother reared-MR) or without mothers (AR) from postnatal day (PND) 3. AR rats received three different treatments: (1) AR-CONTROL group received minimal tactile stimulation, (2) AR-ODOR females received exposure to maternal nest material inside the AR-isolation-cup environment, (3) AR-SOCIAL group was reared in the cup with maternal nest material and a conspecific of the same-age and same-sex and received additional tactile stimulation. MR females were reared by their mothers in the nest and with conspecifics. In adulthood, rats were tested for maternal behavior towards their own pups and in a social learning task. Results confirm our previous report that AR impairs performance of maternal behavior and the development of a social food preference. Furthermore, social cues from a littermate, in combination with tactile stimulation and the nest odor, reversed the negative effects of complete isolation (AR-CONTROL) on some of the above behaviors. Exposure to the odor alone also had effects on some of these olfactory-mediated behaviors. These studies indicate that social stimulation from littermates during the preweaning period, in combination with odor from the nest and tactile stimulation, contributes to the development of affiliative behaviors.

Age Factors↗
PubMed2004

Epstein-Barr virus seroreactivity among unaffected individuals within high-risk nasopharyngeal carcinoma families in Taiwan.

Most adults have been infected with EBV. Many studies have indicated that antibodies against specific EBV antigens, particularly IgA antibodies, can be predictive or prognostic of EBV-associated malignancies, such as NPC. We hypothesized that healthy individuals from families with a history of multiple members affected with NPC (who therefore might be genetically susceptible to NPC themselves) might have an EBV antibody profile that is distinct from that seen in healthy individuals from the community at large. To explore this possibility and examine determinants of anti-EBV antibody levels in healthy, high-risk individuals, we evaluated data from 2 parallel studies of NPC in Taiwan, which included 1,229 healthy members of families in which 2 or more individuals were affected with NPC and 320 controls from the community at large. Blood collected from participants was tested for IgA antibodies against EBV VCA and EBNA-1 and for neutralizing antibodies against EBV DNase using standard assays. We observed evidence of familial aggregation of EBV seroreactivity among individuals from high-risk, multiplex NPC families. Anti-VCA IgA and anti-EBNA-1 IgA antibody seroprevalence in unaffected family members of NPC cases was 5-6 times higher than in members of the community (p < 0.01). This elevated seroprevalence among unaffected individuals from high-risk families was observed regardless of the relationship of the unaffected individual to the closest affected relative (siblings, parents, children or spouses). No sociodemographic or environmental factors examined were found to strongly and consistently correlate with elevated seroprevalence, but patterns emerged of increasing seroprevalence among older individuals and among females. Unaffected individuals from high-risk NPC families have elevated anti-EBV IgA antibody titers. The etiologic and clinical implications of this finding remain to be established.

Adolescent↗
PubMed2007

Experiences of siblings of patients with Fanconi anemia.

BACKGROUND: Clinical management of families with autosomal recessive genetic disorders focuses almost exclusively on the affected family members. However, clinically unaffected members of such families may also be severely troubled by the serious illness in a family member. The purpose of this study was to explore the experiences of healthy siblings of patients with a chronic genetic disease, Fanconi Anemia (FA). PROCEDURE: We used a qualitative, descriptive design, which consisted of in-depth, semi-structured interviews. A convenience sample of nine siblings of patients with FA was recruited from a National Cancer Institute clinical research protocol, which targets families with inherited bone marrow failure syndromes. NVivo 2.0 software facilitated qualitative content analysis of the data. RESULTS: Siblings' rich descriptions provided novel insights into the intricate hardships of living within a family in which a rare, life-threatening, chronic genetic illness in one member is the focus of daily life. Four major themes of the sibling experience emerged from the interview data: (1) containment, (2) invisibility, (3) worry, and (4) despair. CONCLUSIONS: Our data suggest that unrecognized psychosocial issues exist for the apparently healthy siblings of patients with FA. This study explores the psychosocial consequences of living in a family with FA and one of only a few studies to explore the sibling experience of chronic illness using a contemporaneous approach. These findings support the need for an increased awareness among health care providers; future hypothesis driven investigation, and improved assessment of problems with potential psychological morbidity.

Adolescent↗
PubMed1981

Aggressive behavior in normal and deviant members of intact versus mother-only families.

Single-parent families have been identified as using more coercion and aggression to elicit compliance than intact families. The present study compared 9 mother-only and 15 intact families from a referred clinical sample to 9 mother-only and 16 intact nonreferred "normal" families using a family behavioral observation code. Clinical families emitted higher rates of aggressive behavior than normals, and mother-only emitted higher rates than intact. However, mother-only normals had lower rates than intact clinical families. The intact versus mother-only factor appears to be less important in understanding aggression than do the specific interactional patterns of family members.

Aggression↗
PubMed1995

The childhood and family dynamics of transvestites.

This article reports a survey of childhood experiences and family dynamics reported by a sample of 85 cross-dressing males drawn from the readership of a magazine for transvestites. The sample had a higher percentage of only children and eldest children compared to a national sample and also a much closer relationship with their mothers than with their fathers. Their identification as nuclear or marginal transvestites or transsexuals is related to the quality of the reported relationship with the mother, to the factors they identify as associated with their cross-dressing, and to their sexual orientation. Covert cross-dressers account for over three fourths of the subjects, but those who were overt (their cross-dressing openly encouraged by female family members) show significantly different patterns and distributions on several variables. A constellation of family and parental relationships is proposed--drawn in part from the insights of object relations and family systems theory--which may contribute to the development of transvestism.

Adult↗
PubMed1996

Helping children cope when a family member has cancer.

A cancer diagnosis impacts the entire family unit, but children are especially vulnerable. In the past, families and professionals did not share information or allow for children to express their feelings or to be involved. Children have the right to know and the need to know the truth. Interventions should be based on both the developmental stage of the child and the stage of the illness. Approaches by disease phase and developmental stage are discussed. Goals include maintaining family stability, preparing children for what may happen, allowing for flexible communication, and preventing serious psychosocial sequelae.

Adaptation, Psychological↗
PubMed1996

The accessory gland proteins in male Drosophila: structural, reproductive, and evolutionary aspects.

Recent results from biochemical and molecular genetic studies of the accessory gland proteins in male Drosophila are reviewed. The most prominent feature is the species-specific variability. However, the analysis of the sex peptide in D. melanogaster shows that there is a strong homology in the molecular structure to the closely related sibling species, and that divergence increases with increasing phylogenetic distance. For this reason the sex peptide, after being transferred to the female genital tract during copulation, reduces receptivity and increases oviposition only in virgin females belonging to the same species group and subgroup. Even though studies were hitherto limited to a small number of the secretory components, it is evident that the accessory gland proteins play a key role in reproductive success of the fruit fly by changing female sexual behavior, supporting sperm transfer, storage and displacement. Thus, genes encoding the accessory gland proteins are apparently under strong evolutionary selection.

Animals↗
PubMed2004

Feasibility of a cost-effective approach to evaluate short tandem repeat markers suitable for chimerism follow-up.

BACKGROUND: Precise chimerism monitoring is important for the prediction of the success of allogeneic bone marrow transplantation (BMT). Most of the current procedures employed for chimerism follow-up with short tandem repeat (STR) markers are either time-consuming, labor-intensive, or use expensive assays, making it burdensome to perform large-scale studies of transplanted patients. AIM: To set-up a simple nonradioactive method to investigate a set of STR markers that could be used in the evaluation of chimerism status after allogeneic BMT. METHOD: Six dinucleotide STRs (D2S123, D5S107, CRTL1, D7S500, D11S1356, and TP53) were analyzed by touchdown (TD)-PCR followed by medium size non-denaturing polyacrylamide gel electrophoresis and silver staining. The sensitivity of the approach was evaluated by dilution competition assays. Peripheral blood samples were taken from a group of 50 healthy Argentinean donors, two transplanted patients, and their respective bone marrow donors. Buccal mucosa samples were also obtained from the BMT recipients. RESULTS: Four markers, D2S123, D7S500, D11S1356, and TP53, presented the highest heterozygosities (0.67-0.88) under our experimental system. A sensitivity of 0.8-1.6% for chimerism detection was consistently found for the different STR. The usefulness of these STR in chimerism analysis was illustrated with the screening of related siblings analyzing two transplanted patients with persistent mixed chimerism, which were previously studied by fluorescence in situ hybridization (FISH). Similar proportions of mixed chimerism were obtained with STR analysis compared with those estimated by FISH. DISCUSSION: To our knowledge, this was the first study of mixed chimerism using TD-PCR to achieve a highly specific STR amplification. This approach allows simple and accurate chimerism quantification because it avoids slippage of Taq polymerase on repeat stretches and prevents the differential amplification of the shorter allele. STR heterozygosities and the high level of sensitivity of this method demonstrated that this approach is not only very informative in this population, but is also rapid (taking less than 14 hours) and cost-efficient. CONCLUSION: The data confirms that this method is a useful tool applicable to routine large-scale STR genotyping and mixed chimerism analysis in low-complexity laboratories worldwide.

Bone Marrow Transplantation↗
PubMed1998

Evolutionary history and mechanism of the Drosophila cecropin gene family.

Upon bacterial infection, insects secrete a set of synthesized antibacterial proteins into the hemolymph and initiate synergistic destruction of invaders. Cecropin is one such antibacterial protein which is also found in vertebrates. To study the evolutionary history and mechanism of the Cecropin gene family, we determined DNA sequences of one isogenic In(3R)C and six isofemale lines of Drosophila melanogaster as well as one line of D. simulans and of D. yakuba. The phylogenetic analysis of these sequences together with those published for D. virilis and Sarcophaga peregrina reveals frequent gene re-organization. It was also found that silent nucleotide differences within D. melanogaster are quite heterogeneous across the gene region of approximately 3 kilobases and the extent of polymorphism is unusually usually high. These data suggest that the Cecropin gene region of D. melanogaster underwent intragenic recombination as well as introgression from a closely related sibling species, D. simulans.

Animals↗