Incomplete DJH rearrangements as a novel tumor target for minimal residual disease quantitation in multiple myeloma using real-time PCR.

The hypervariable regions of immunoglobulin heavy-chain (IgH) rearrangements provide a specific tumor marker in multiple myeloma (MM). Recently, real-time PCR assays have been developed in order to quantify the number of tumor cells after treatment. However, these strategies are hampered by the presence of somatic hypermutation (SH) in VDJH rearrangements from multiple myeloma (MM) patients, which causes mismatches between primers and/or probes and the target, leading to a nonaccurate quantification of tumor cells. Our group has recently described a 60% incidence of incomplete DJH rearrangements in MM patients, with no or very low rates of SH. In this study, we compare the efficiency of a real-time PCR approach for the analysis of both complete and incomplete IgH rearrangements in eight MM patients using only three JH consensus probes. We were able to design an allele-specific oligonucleotide for both the complete and incomplete rearrangement in all patients. DJH rearrangements fulfilled the criteria of effectiveness for real-time PCR in all samples (ie no unspecific amplification, detection of less than 10 tumor cells within 10(5) polyclonal background and correlation coefficients of standard curves higher than 0.98). By contrast, only three out of eight VDJH rearrangements fulfilled these criteria. Further analyses showed that the remaining five VDJH rearrangements carried three or more somatic mutations in the probe and primer sites, leading to a dramatic decrease in the melting temperature. These results support the use of incomplete DJH rearrangements instead of complete somatically mutated VDJH rearrangements for investigation of minimal residual disease in multiple myeloma.     

Heparin treatment reduces glomerular injury in rats with adriamycin-induced nephropathy but does not modify tubulointerstitial damage or the renal production of transforming growth factor-beta

In this study we investigated the effect of heparin on renal injury and renal transforming growth factor-beta (TGF-beta) production in adriamycin (AD)-injected rats. Thirty-nine female Wistar rats were injected with AD (3.5 mg/kg body weight, i.v.) and 27 with 0.15 M NaCl solution (group C). Fifteen days later we started to inject heparin, 500 U/day, s.c., in 20 of the AD-injected animals (AD-H group). Three months after beginning treatment, urine samples were collected to quantify albumin, creatinine and TGF-beta. The rats were killed and the kidneys removed for histological, immunohistochemical, ELISA and RNA studies. All AD-injected animals showed structural renal changes (p < 0.05). However, the glomerular alterations were less intense in rats from group AD-H (p < 0.05). The percentage of glomerulosclerosis was 0.11 +/- 0.08 in group C, 14.7 +/- 12.8 in group AD (treated only with AD) and 3.42 +/- 2.3 in group AD-H. Renal cortex immunostaining for TGF-beta and mRNA content of this polypeptide was higher in both groups of animals injected with AD compared to controls (p < 0.05). These animals also presented a higher rate of urinary TGF-beta excretion (p < 0.05), which was 202 +/- 11 in group C, 1,103 +/- 580 in group AD and 1,564 +/- 328 pg/mg Ucreat in group AD-H. However, TGF-beta activity in the glomerular-conditioned media from the rats of group AD was higher than in the glomerular-conditioned media from the rats of group AD-H. In conclusion, treatment with heparin reduces glomerular damage in rats with AD-induced nephropathy but does not modify tubulointerstitial lesions or the renal production of TGF-beta.     

Adult height in patients with childhood onset atopic dermatitis

Cross sectional studies have reported impaired growth in children with atopic dermatitis. If this growth impairment is irreversible, it would be expected to adversely influence final height attainment. The standing heights and other anthropometric parameters were assessed in 35 adults with onset of atopic dermatitis before 5 years of age and a control group of 35 adults with adult onset contact dermatitis or psoriasis. There was no significant difference in the standing height SD score, mid-parental height SD score, sitting height SD score, subischial leg length SD score, nor body mass index between the atopic dermatitis and control groups. The standing height SD score was not significantly different among: (a) patients with atopic dermatitis affecting less than 50% of their body surface area and those with greater than 50% affected; (b) patients using the four different potency topical corticosteroids; and (c) patients with atopic dermatitis without asthma and those with coexisting asthma. It is concluded that short stature is not a feature of our group of adult patients with onset of atopic dermatitis before 5 years of age, continuing into adulthood, and severe enough to require specialist care. This suggests that if growth impairment occurs in childhood, it is likely to be temporary and reversible.     

Safety Behaviors of Abused Women After an Intervention During Pregnancy

Objective: To evaluate an intervention protocol, administered during pregnancy, for increasing safety-seeking behaviors of abused women.
Design: Prospective, ethnically stratified cohort analysis.
Setting: Public prenatal clinics.
Participants: Pregnant women reporting physical or sexual abuse in the year before or during the present pregnancy. One hundred thirty-two women met study criteria, received the intervention, and were followed for 1 year after the completion of the pregnancy.
Intervention: Three education, advocacy, and community referral sessions that included information on safety behaviors.
Main outcome Measure: Adoption of safety behaviors by abused women. Safety behaviors were measured before the intervention, twice during pregnancy, and at 2, 6, and 12 months after completion of the pregnancy.
Results: Repeated measures analysis of variance showed a significant increase in adoption of each safety behavior (p < .0001), with most behaviors showing a significant increase after the first intervention session.
Conclusions: Pregnant women who were abused and were offered an intervention protocol report a significant increase in safety behavior adoption during and after pregnancy. Abuse during pregnancy is common. Identification of abuse and immediate clinical intervention that includes information about safety behaviors can result in safety behavior adoption that may prevent future abuse and increase the safety and well-being of women and infants.     

Patterns of sediment dispersion coastwise the State of Bahia - Brazil

Using the average directions of the main wave-fronts which approach the coast of Bahia State - coinciding with that of the main wind occurring in the area - and of their periods, we define a wave climate model based on the construction of refraction diagrams. The resulting model of sediment transport was able to reproduce, in a general way, the sediment dispersion patterns furnished by geomorphic indicators of the littoral drift. These dispersion patterns control the generation of different types of sediment accumulations and of coastal stretches under erosion. We demonstrate that the presence of the Abrolhos and Corumbaú Point coral reefs is an important factor controlling the sediment dispersion patterns, since them act as a large protection against the waves action.     

Beacon: a novel gene involved in the regulation of energy balance

The hypothalamus plays a major role in the control of energy balance via the coordination of several neuropeptides and their receptors. We used a unique polygenic animal model of obesity, Psammomys obesus, and performed differential display polymerase chain reaction on hypothalamic mRNA samples to identify novel genes involved in obesity. In this study, we describe a novel gene that encodes a small protein we have termed "beacon." Beacon mRNA gene expression in the hypothalamus was positively correlated with percentage of body fat. Intracerebroventricular infusion of beacon resulted in a dose-dependent increase in food intake and body weight and an increase in hypothalamic expression of neuropeptide Y (NPY). Simultaneous infusion of beacon and NPY significantly potentiated the orexigenic response and resulted in rapid body weight gain. These data suggest a role for beacon in the regulation of energy balance and body weight homeostasis that may be mediated, at least in part, through the NPY pathway.     

Survey of forensic psychiatrists on evaluation and treatment of prisoners on death row

Psychiatrists have debated their role in evaluating prisoners accused of capital crimes and in treating prisoners on death row when restoration of competence would result in execution. Despite debate, there are no previous surveys of psychiatrists' opinions on this issue. We sent an anonymous questionnaire to all board-certified forensic psychiatrists in the United States. Of the 456 forensic psychiatrists identified, 290 (64%) returned the survey. Most respondents supported a role, in at least some cases, for psychiatric evaluation of prisoners accused of capital crimes. Respondents were divided on whether or not psychiatrists should treat incompetent death row prisoners if restoration of competence would result in execution. Attitudes about the ethical acceptability of capital punishment were associated with views about the psychiatrists' role but were not determinative in every case.     

Evidence for dual effects of nitric oxide in the forced swimming test and in the tail suspension test in mice

L-Arginine (L-Arg), a substrate for nitric oxide synthase (NOS) at a dose of 250-500 mg/kg, i.p., significantly reduced the duration of immobility both in the forced swimming test (FST) and in the tail suspension test (TST), two models of depression in mice, without changing locomotion in an open field. Paradoxically, a similar effect was observed with the administration of N(G)-nitro-L-arginine (L-NNA) (0.3-10 mg/kg, i.p.), an inhibitor of NOS. However, higher doses of L-Arg (750-1000 mg/kg) and L-NNA (30 mg/kg) did not produce any anti-immobility effect in FST and TST. The inactive isomers D-Arg (100-1000 mg/kg, i.p.) and D-NNA (0.3-30 mg/kg, i.p.) did not affect immobility duration in either the FST and TST. Preadministration of L-NNA (30 mg/kg, i.p.), but not of D-NNA completely blocked the anti-immobility effect of L-Arg (500 mg/kg, i.p.) in the FST. Similarly, L-Arg (750 mg/kg, i.p.), but not D-Arg blocked the anti-immobility effect of L-NNA (3 mg/kg, i.p.) in the FST. The results indicate that either the synthesis of NO or the inhibition of its synthesis may produce antidepressant-like effects when assessed in the FST and TST. The physiological meaning of this finding is still obscure, but it could indicate that NO has a dual role in the modulation of depression.