Camp Okizu: Preliminary Investigation of a Psychological Intervention for Siblings of Pediatric Cancer Patients

This research was conducted at a summer camp for siblings of children with cancer. The camp is designed to address emotional problems, provide peer interaction and validation, and bolster siblings' self-esteem. Standardized measures assessing posttraumatic stress, anxiety, quality of life, and self-esteem were administered to 77 siblings (ages 6-17) prior to attending camp and again 3 months after camp. From pre- to post-camp, the siblings reported statistically significant decreases in symptoms of posttraumatic stress and anxiety, and statistically significant improvements in quality of life and self-esteem. These preliminary findings are encouraging and suggest the value of camp as a psychological intervention and provide a model for other pediatric cancer facilities designing intervention programs for siblings.     

Testicular amplificaion and impaired transmission of human butyrylcholinesterase cDNA in transgenic mice

Gene amplification occurs frequently in tumour tissues yet is,in general, non-inheritable. To study the molecular mechanismsconferring this restraint, we created transgenic mice carryinga human butyrylcholinesterase (BCHE) coding sequence, previouslyfound to be amplified in a father and son. Blot hybridizationof tail DNA samples revealed somatic transgene amplificationswith variable restriction patterns and intensities, suggestingthe occurrence of independent amplification events, in 31% (11/35)of mice from the FII generation but in only 3.5% (2/58) of theFII and FIV generations. In contrast, >10-fold amplificationsof the BCHE transgene and the endogenous acetylcholinesteraseand c-raf genes appeared in both testis and epididymis DNA from>80% of FIII mice. Drastic, selective reductions in testisBCHEmRNA but not in actin mRNA were detected by the PCR amplificationof testis cDNA from the transgenic mice, and apparently resultedin the limited transmission of amplified genes. The testicularamplification of the BCHE transgene may potentially representa general phenomenon with clinical implications in human infertility.     

Pentylenetetrazole-induced kindling is prevented by prior treatment with cysteamine

We have previously demonstrated that in pentylenetetrazole (PTZ)-kindled rats, cysteamine causes prolonged depression of the kindled state. We now report that administration of cysteamine before or during the kindling process prevents attainment of the kindled state. This effect lasts long after cysteamine administration has ceased, suggesting that depletion or somatostatin may not be the only mechanism underlying cysteamine's effect on kindling. The results also support the likelihood that PTZ kindling primarily effects neocortical rather than limbic structures.     

CAG repeat polymorphism within the KCNN3 gene is a significant contributor to susceptibility to anorexia nervosa: a case-control study of female patients and several ethnic groups in the Israeli Jewish population.

The human small-conductance Ca(2+)-activated potassium channel gene KCNN3 has been involved in mechanisms underlying neuronal function and plasticity. A multiallelic CAG repeat polymorphism within the KCNN3 has been associated with schizophrenia and bipolar disorder. We have previously reported in a family-based study that longer CAG repeats are preferentially transmitted to patients with anorexia nervosa (AN). The present study extends the analysis of KCNN3 allele distribution to a larger series of AN female patients and control groups, incorporating information on ethnicity and co-morbidities associated with AN. The data analysis is presented while considering separately the two alleles of each individual, namely a minor (shorter) and a major (longer) allele. This study has found that the KCNN3 allele distribution in the general Israeli population does not differ significantly in at least four Jewish ethnic groups of Ashkenazi, North African, Iraqi, and Yemenite origin. These have been used as control groups in a matched case-control analysis that has demonstrated a significant over-representation of KCNN3 alleles with longer CAG repeats among AN patients (P < 0.001 for the major allele and P = 0.035 for allele sum). Under dichotomization, a significantly higher prevalence of the L allele (>19 repeats) has been observed among AN patients (P < 0.001). While considering AN and co-morbid phenotypes, a tendency towards longer (L) alleles has been observed in the subset of patients with obsessive-compulsive disorder (OCD) co-morbidity. These findings further implicate KCNN3 as a significant contributor to predisposition to AN.     

Pneumococcaemia as a presenting sign in 3 cases of multiple myeloma

Multiple myeloma was diagnosed in 3 patients following episodes of pneumococcaemia associated with neutropenia and decreased serum concentration of normal immunoglobulins. Severe pneumococcal infection is commonly encountered during the course of multiple myeloma, but has not been stressed as a presenting feature of the disease.     

Spontaneous increase of DNA turnover in murine systemic lupus erythematosus

DNA synthesis and release was studied in unstimulated splenocytes of strains of mice known to develop spontaneous systemic lupus erythematosus (SLE)-like disease and in non-SLE age- and sex-matched strains as well. Newly synthesized DNA was measured as total acid-insoluble radioactive material present in cell pellet plus supernatant of unstimulated 0–72 h cell cultures [³H]thymidine-pulsed, whereas DNA release was measured as amount of acid-precipitable radioactivity found in supernatant of those cultures. In all strains known to develop spontaneous murine SLE the amount of newly synthesized DNA was 1.3–2.1-fold increased when compared to normal strains studied concomitantly. Furthermore, a significant increase in DNA release into medium, unrelated to cell viability, was observed in those strains as well. These observations clearly demonstrate different metabolic rates of synthesis and release of DNA in murine SLE. This difference suggests the existance of an underlying mechanism responsible for extracellular DNA abundancy, which may be important for the formation of circulating DNA-anti-DNA immune complexes.     

Subcellular morphological changes in the rat kidney after phosphorus burn.

Experimental phosphorus burns were performed on male rats, in order to evaluate the subcellular changes which had occurred as a result of their lesions. In addition to the external wound caused by the burn itself, pathological changes were observed macroscopically and microscopically in various body organs, mainly the kidneys. These were investigated under the electron microscope for subcellular alterations at their damaged sites, and for biochemical aberrations that were observed in those rats. In the phosphorus-burnt rats the glomeruli were ischemic, showed capillary collapse and exhibited proliferation of mesangial areas and basement membrane thickening. Many necrotic cells were observed in the proximal tubule, where large vacuoles containing myelin-like structures were identified. The lumen of the proximal tubules were completely occluded by cell debris and the cytoplasm was necrotic. Due to the damage caused to the glomeruli, high concentrations of serum urea, serum SGPT and PO-4 were assayed in the phosphorus-burnt rats. These changes may account for the high mortality rate after phosphorus burns and may further understanding of the damage as well as ways of approaching it.     

Sequential Measurements of Human Decidua-Associated Protein (hDP) 200 in the Uterine Fluid During the Menstrual Cycle

PROBLEM: To examine the relationship between the concentration of uterine fluid human decidua-associated protein (hDP) 200, identified as a monoclonal rheumatoid factor, and different phases of the menstrual cycle. METHODS: Sequential measurements of hDP 200 concentration in uterine fluid were performed in 11 normal ovulatory women, aged 22–36 years. The samples were collected in early proliferative phase, late proliferative phase, periovulatory period, early secretory phase, and late secretory phase. RESULTS: Consistent fluctuations of hDP 200 levels in uterine fluid were found throughout the menstrual cycle. High levels were found during early proliferative phase and periovulatory period related to significantly lower levels during late proliferative and early luteal phases. CONCLUSION: There is menstrual phase dependent variation in the uterine fluid levels of hDP 200.     

Production of neurotrophins by activated T cells: implications for neuroprotective autoimmunity

Neurotrophins (NTs) promote neuronal survival and maintenance during development and after injury. However, their role in the communication between the nervous system and the immune system is not yet clear. We observed recently that passively transferred activated T cells of various antigen specificities home to the injured central nervous system (CNS), yet only autoimmune T cells specific to a CNS antigen, myelin basic protein (MBP), protect neurons from secondary degeneration after crush injury of the rat optic nerve. Here we examined the involvement of NTs in T-cell-mediated neuroprotection, and the possible significance of the antigen specificity of the T cells in this activity. Analysis of cytokine and NT expression in various rat T cell lines showed that the T cells express mRNA for cytokines of Th1, Th2, and Th3 phenotypes. In addition, the T cells express mRNA and protein specific to nerve growth factor, brain-derived neurotrophic factor, NT-3, and NT-4/5. Antigen activation significantly increased NT secretion. Thus, reactivation of CNS autoimmune T cells by locally presented antigens to which they are specific can lead to enhanced secretion of NTs and possibly also of other factors in injured optic nerves. mRNA for TrkA, TrkB and p75 receptors was expressed in the injured nerve, suggesting that these specific receptors can mediate the effects of the T-cell-derived NTs. The neuroprotective effect of the passively transferred autoimmune anti-MBP T cells in injured optic nerves was significantly decreased after local applicaiton of a tyrosine kinase inhibitor known to be associated with NT-receptor activity. These results suggest that the neuroprotective effect of autoimmune T cells involves the secretion of factors such as NTs by the T cells reactivated by their specific antigen in the injured CNS. T cell intervention in the injured CNS might prove to be a useful means of promoting post-injury CNS maintenance and recovery, possibly via supply of NTs and other factors.