Partial trisomy 6p and partial monosomy 9p from a de novo translocation 46, XY, -9, + DER(9)T(6:9)(p211:p24)

This report describes an adult male with a partial trisomy 6p(p211-pter) and a partial monosomy 9p(9p24-pter) resulting from a de novo unbalanced translocation. This patient does not show the classical featured of the 9p partial monosomy syndrome, thus disputing the claim of Hoo et al. (1982) that 9p24 is the critical segment for the monosomy syndrome. Partial trisomy for 6p has only been previously reported in children. In addition to the chromosomal anomalies, the patient has autosomal recessive spinal muscular atrophy with a different age of onset than two affected sibs. Finally, he shows unusual audiologic and ophthalmologic signs nor previously reported as part of the 9p monosomy or 6p trisomy syndromes.     

Generation and characterization of a clonotypic antibody specific for the T cell receptor of an arthritogenic T cell clone--studies in adjuvant arthritis

Adjuvant Arthritis (AA) can be induced by passive transfer of a T cell clone (A2b) derived from arthritic rats, specific for Heat Shock Protein 60, HSP60 176-190. Furthermore, a crucial role for T cells with HSP60 176-190 specificity in AA was shown by induction of tolerance using HSP60 176-190 or by immunization with an altered peptide ligand based on the same sequence. To study clonal expansion of A2b-like T cells during AA and to determine their role in AA induction, we generated a clonotypic antibody, 16C4, specific for the TCR of the A2b T cell clone (TCR AV11S1/BV18). This antibody stained A2b T cells in flow cytometry experiments, induced proliferation of A2b cells when fixed on a solid support, and inhibited antigen-induced A2b proliferation when added in solution. A2b-like T cells were detected in a low frequency in lymphoid organs of arthritic rats. Thus, as in vivo administration of 16C4 did not inhibit AA, cells containing the determinant recognized by 16C4 are possibly not the sole contributors to AA development. Furthermore, epitope specific interventions by antigen administration may be possible even in cases where the epitope specific T cell clonotype is of low frequency.     

Heat-shock proteins in autoimmune arthritis: a critical contribution based on the adjuvant arthritis model

Recognition of self protein epitopes, apart from those engaged in idiotypic network interactions and MHC restriction, is probably a physiological event in the normal functioning immune system. Furthermore T and B cells recognizing self antigens can be easily cloned from healthy individuals and sometimes be shown to confer autoimmune disease by passive transfer in the experimental situation. The issue is how potentially autoaggressive cells can become activated and how such activity can be contained safely. Experimentally, autoimmune disease can be evoked by immunization with autoantigens (encephalomyelitis, thyroiditis etc.) or with foreign antigens that feature antigenic relationships with self antigens (adjuvant arthritis). In both situations transfer of disease has been shown with cloned T cells of a single specificity. In addition, specific control of disease using the same cloned T cells has been achieved. Adjuvant arthritis has been illustrative in these respects. By means of specificity analysis of cloned T cells, a 65 kD heat shock protein of mycobacteria was identified as crucial in the disease. Immunization with this antigen has been found to prevent the development of disease, including forms elicited without mycobacterial involvement. Furthermore, vigorous immunological responses to HSP65 were found both in experimental animals and also in humans as a consequence of exposition to various infectious organisms. By their conserved nature HSPs have ample potential for dangerous mimicry. Recent evidence accumulated suggesting that the same HPS65 may be crucial in human chronic arthritis as well. Therefore it is hoped that extrapolation of the experimental findings to the human situation will help the development of specific means, either T cells or antigens, to control spontaneous autoimmune arthritis in man.     

A phase II study of ifosfamide in children with recurrent solid tumours

Summary Twenty children with recurrent or unresponsive tumours (10 Wilms', 3 rhabdomyosarcoma, 4 Ewings's, 1 osteosarcoma, 1 hepatoblastoma, 1 hepatoma) and one untreated patient with renal carcinoma were given ifosfamide as a 24-h infusion (5 mg/m²), with mesna as uroprotective. The number of courses ranged from 1 to 13 (median 3), and the interval between them was 2–3 weeks. Sixteen of these patients had previously received cyclophosphamide. Complete clinical responses were seen in 3 cases (2 Wilms' and 1 Ewing's) and lasted 5, 7, and 9 months. Partial responses were seen in 3 instances, mixed response or stable disease in 4, and progressive disease in 11. Treatment was well tolerated in most patients, with no cystitis or severe myelosuppression, but 2 children developed transient neurological symptoms and 1 became hypertensive. Nausea and vomiting were controlled by high-dose dexamethasone in most children.Plasma ifosfamide levels were estimated by means of gas-liquid chromatography in 10 patients. Peak concentrations ranged from 38 to 125 g/ml (median 80). The elimination half-life, at 2.5–5.2 h (median 3.2) was shorter than previously reported in adults.Future studies should test the possibility that ifosfamide-containing combination chemotherapy may be more effective than the regimens, usually including cyclophosphamide, that are currently used as front-line treatment of embryonal and Ewing's sarcoma.     

Online health communities,contributions to caregivers and resilience of older adults

The aim of this paper is twofold. Firstly, to investigate the potential benefits of online health communities (OHCs) for informal caregivers by conducting a systematic literature review. Secondly, to identify the relationship between the potential benefits of OHCs and resilience factors of older adults. Performing a thematic analysis, we identified the potential benefits of OHCs for informal caregivers of older adults, including two salient themes: (a) caregivers sharing and receiving social support and (b) self and moral empowerment of caregivers. Then, we uncovered how these potential benefits can support resilience of older adults. Our findings show that sharing and receiving of social support by informal caregivers, and self and moral empowerment of informal caregivers in OHCs, can support four resilience factors among older adults, including self-care, independence, altruism and external connections. This review enables a better understanding of OHCs and Gerontology, and our outcomes also challenge the way healthcare and aged-care service providers view caregivers and older adults. Furthermore, the identified gap and opportunities would provide avenues for further research in OHCs.     

Elucidating chromatin and nuclear domain architecture with electron spectroscopic imaging

Electron microscopy has been the ‘gold standard’ of spatial resolution for studying the structure of the cell nucleus. Electron spectroscopic imaging (ESI) offers advantages over conventional transmission electron microscopy by eliminating the need for heavy-atom contrast agents. ESI also provides mass-dependent and element-specific information at high resolution, permitting the distinguishing of structures that are primarily composed of protein, DNA, or RNA. The technique can be applied to understand the structural consequences of epigenetic modifications, such as modified histones, on chromatin fiber morphology. ESI can also be applied to elucidate the multifunctional behavior of subnuclear ‘organelles’ such as the nucleolus and promyelocytic leukemia nuclear bodies. The authors dedicate this paper to the memory of Ying Ren (1961–2007). We all benefited from knowing her. Our research advanced through the technical creativity she provided.     

Recommendations on the use of colony-stimulating factors in children: conclusions of a European panel

During 1996 and 1997 a panel of European haematologists, oncologists, and neonatologists developed specific paediatric guidelines for the use of colony stimulating factors based on published literature and the clinical experience of these specialists within each of 13 countries. Well established indications for use comprise intervention in patients with life-threatening infection, adjunctive therapy post autologous bone marrow transplantation (BMT), mobilization of peripheral blood progenitor cells for autologous BMT, patients with acquired aplastic anaemia on anti-lymphocyte globulin and cyclosporin regimen, and severe congenital neutropenia. Less clear indications include primary prophylaxis to support dose intensification in children with high risk/advanced malignancies, secondary prophylaxis to prevent neutropenia in patients with a history of severe neutropenia, support therapy in cases of poor marrow function following BMT and for deteriorating marrow function following successful BMT, in neonatal sepsis and non infectious neonatal neutropenia, in drug induced neutropenia and in HIV-positive patients. Treatment is generally well tolerated and granulocyte colony stimulating factor appears better tolerated than granulocyte and macrophage colony stimulating factor. Economically colony stimulating factors have not been shown to induce excessive costs for a given patient. Conclusion In general the adult guidelines are applicable to children but additional considerations (aggressive or very progressive childhood neoplasms, specific indications, neonatal use, congenital disorders) must be taken into account. Received: 21 October 1997 and in revised form: 30 April 1998 /Accepted: 5 May 1998     

Matching risk and resources in high-risk pregnancies.

OBJECTIVE: To evaluate the joint impact of pregnancy risk and the timing of referral of high-risk pregnancies from obstetricians to maternal fetal medicine (MFM) sub-specialists on gestational age (GA) at delivery. METHODS: For the period 1992-2002, 2567 consecutive deliveries from pregnancies of at least 23 weeks gestational age (GA) from a community-level sub-specialty perinatal center were studied. A multiple regression model was developed specifying the impact of various risk factors and referral timing. RESULTS: Prior pregnancy risk was inversely related to GA at birth. Referral timing, operationalized as a continuous variable, did not have a significant additive impact on GA at birth, but several dummy-variable interaction effects combining risk factors and referral before 20 weeks as a dichotomy were significant. CONCLUSION: There are identifiable risks that occur either before the pregnancy or early into it that should lead to early referral to a sub-specialist because of their impact on GA at birth. Early referral is an important tactic in a larger preterm prevention strategy, but it needs to be embedded in a broader maternal-fetal health initiative in which both generalists and sub-specialists play important roles.     

Menopausal symptoms in a hospital-based sample of women in southern Thailand.

OBJECTIVE: To evaluate menopausal symptoms and quality of life in middle-aged women. STUDY DESIGN: Hospital-based, cross-sectional study. METHODS: A survey was conducted among 270 women aged 45-65 years who attended the gynecological and menopause clinic, Songklanagarind Hospital. We used the MENQOL questionnaire as the instrument. RESULTS: The average age at menopause of the postmenopausal women was 48.7 years (range 40-57 years). The prevalences of the classical menopausal symptoms--hot flushes, night sweats, and vaginal dryness--in the women aged 45-65 years were 36.8%, 20.8 and 55.3%, respectively. The three most prevalent symptoms in perimenopause were aching in muscles and joints, experiencing poor memory, and change in sexual desire. Within the four domains (vasomotor, psychological, physical, and sexual symptoms), more suffering was reported in the perimenopausal and postmenopausal subjects than in the premenopausal subjects (p < 0.001). CONCLUSIONS: Peri- and postmenopausal women had a significant decrease in quality of life compared to premenopausal women.