Catecholaminergic neurons in the brain-stem and sleep apnea in SIDS victims

Background: Tyrosine hydroxylase (TH) is a specific marker for catecholaminergic neurones. Some reports have demonstrated a decrease of TH in the sudden infant death syndrome (SIDS) compared with controls. To further investigate this, the correlation between TH and sleep apnea was investigated here. Materials and methods: Among 27,000 infants studied prospectively to characterize their sleep–wake behavior, 38 infants died under 6 months of age. They included 26 cases of SIDS. All the infants had been recorded during one night in a pediatric sleep laboratory some 3–12 weeks before death. The frequency and the duration of sleep apnea were analyzed. The brain-stem material was collected and subjected to immunohistochemical studies for TH. The density of TH-immunoreactive neurons was measured in the nucleus hypoglossus, nervus vagus dorsalis, solitary and ambiguus and the ventrolateral medulla (VLM) in the medulla oblongata. Correlation analyses were carried out between the density of TH-immunoreactive neurons and the data from the sleep apnea studies. Results: There was no SIDS specific correlation between TH-immunoreactive neurons in the nucleus hypoglossus, nervus vagus dorsalis, solitary and ambiguus and the ventrolateral medulla in the medulla oblongata and the frequency and duration of sleep apnea. Conclusions: No significant association between the pathological data and the physiological data refers to TH-positive neurons in the medulla oblongata in SIDS victims.     

Analysis of the coxsackievirus B-adenovirus receptor gene in patients with myocarditis or dilated cardiomyopathy

Myocarditis and dilated cardiomyopathy (DCM) are common causes of morbidity and mortality in children and adults, most commonly due to infection with coxsackievirus B or adenovirus. Increased expression of the common human coxsackievirus B-adenovirus receptor (CAR) has been reported in patients with DCM. We investigated the CAR gene in patients with acquired or familial myocarditis/DCM for mutations/polymorphisms. Several polymorphisms or intronic substitutions, distant from the intron-exon boundaries, were identified but no mutations. Based upon these data it appears that CAR gene mutations are not a major host determinant in the development of myocarditis and DCM.     

Pattern of spatial distribution inDrosophila melanogaster

The effect of temperature and sex on spatial distribution ofDrosophila melanogaster adults was studied in a specially designed apparatus. It was observed that individuals tend to aggregate in sections of the sphere independently of sex and temperature. Nevertheless, decrease in temperature increase aggregation. The mobility of both males and females indicates a megative geotactic tendency.     

Correlation between the Ki-67 antigen in the brainstem and physiological data on sleep apnea in SIDS victims

Background: The Ki-67 antigen appears in all human proliferating cells during late G1, S, M and G2 phases of the cell cycle, but is consistently absent in the G_o phase (noncycling) cells. The correlation between Ki-67 in the brainstem and sleep apnea in victims of the sudden infant death syndrome (SIDS) was investigated to elucidate cell kinetics in the brainstem of this condition, which is still the main cause of postneonatal infant death. Materials and methods: Twenty-six cases of SIDS occurred among 38 infants dying under 6 months of age in a cohort of 27,000 infants studied prospectively to characterize their sleep–wake behavior. All the infants had been recorded during one night in a pediatric sleep laboratory some 3–12 weeks before death. The frequency and duration of sleep apnea were analyzed. At autopsy, brainstem material was collected and immunohistochemistry for Ki-67 was carried out. The density of Ki-67-positive neurons was measured semiquantitatively. Correlation analyses were carried out between the density of Ki-67-positive neurons and the data on sleep apnea. Results: Except in two cases in SIDS victims and in one control, the detection of Ki-67 was negative. No correlation analysis between the Ki-67 and of sleep apnea was found. Conclusions: There were no abnormal cell kinetics detected by the demonstration of Ki-67 antigen in the brainstems of SIDS victims.     

Isolation and characterization of subgenomic DNAs encapsidated in "single" T = 1 isometric particles of Maize streak virus

"Single" T = 1 isometric particles of Maize streak virus (MSV) have been isolated from infected maize leaves. Biochemical and genetic characterizations show that these particles contain subgenomic (sg) MSV DNA encapsidated by the MSV coat protein. The largest sg DNA is 1.56 kb, slightly larger than half genome size, although sg DNAs as small as 0.2 kb were also cloned. The sg DNAs are not infectious, and they do not appear to play a role in the pathogenicity of MSV. This is the first report of sg DNAs for MSV and, to our knowledge, the first time that encapsidated sg DNAs have been characterized at the sequence level for any geminivirus. These data will assist in our investigations into the role of genomic DNA in the formation of the unique geminate capsid architecture of the Geminiviridae.     

Relevance of HIV-1-specific CD4+ helper T-cell responses during structured treatment interruptions in patients with CD4+ T-cell nadir above 400/mm3

OBJECTIVES: To analyze the dynamics of both HIV-1-specific CD4 and CD8 T-cell responses during structured treatment interruptions (STIs) in chronically HIV-1-infected (CHI) patients and to correlate them with the viral set point achieved. METHODS: Forty-five early-stage CHI patients who were on highly active antiretroviral therapy (HAART) for at least 1 year and underwent STI were included. Plasma viral load (VL), peripheral blood mononuclear cell (PBMC) lymphoproliferative (LPR) response to HIV p24 protein, and HIV-1 epitope-specific interferon-gammarelease from CD8 T cells were measured over a minimum study period of 2 years. RESULTS: VL set point during final STI was both significantly lower than, and positively correlated to, baseline VL (P < 0.0001: mean VL reduction 0.77 log10, and r = 0.42, P = 0.004, respectively). CD4 LPRs to p24 increased significantly (P = 0.001) between day 0 of the first STI cycle and 4th STI but decreased thereafter. VL set point during final STI was significantly and negatively correlated with LPRs to p24 at both 2nd STI and 4th STI. Nevertheless, at week 52, 12 weeks after the end of the last STI, LPRs were weak and transient in all patients and were not correlated with VL set point. Moreover, the magnitude and breadth of HIV-1-specific CD8 T-cell responses increased significantly (P < 0.0001) between day 0 and week 52. The largest increases occurred during the final STI. Even though VL reached set point by week 12 of the final STI, HIV-1-specific CD8 T-cell responses did not stabilize but rather increased until the end of the follow-up and did not correlate with plasma VL (r = 0.01, P = 0.88). CONCLUSIONS: STIs do not lead to control of viral replication in CHI patients, probably due to the fact that boosted CTL responses lack strong and durable helper T-cell responses. To reset the VL set point, new approaches that effectively augment and preserve helper T-cell responses should be investigated.     

Physical Deletion of the p53 Gene in Bladder Cancer: Detection by Fluorescence in Situ Hybridization

To understand better the role of physical p53 deletion in bladder cancer, 106 formalin-fixed and 45 unfixed bladder tumors were examined using fluorescence in situ hybridization. Probes for centromere 17 and the p53 locus were hybridized simultaneously to interphase tumor cells to analyze p53 and chromosome 17 copy number on a cell by cell basis. 17p deletion was found in four of 43 pTa tumors, 18 of 43 pT1 tumors and 29 of 58 pT2-4 tumors (P = 0.0001). 17p deletion was also highly correlated with grade (P = 0.0001) and with p53 immunostaining (P = 0.0005). Chromosome 17 polysomy was associated with stage, grade, 17p deletions, and p53 immunostaining (P = 0.0001). The strong difference in centromere 17 copy number and 17p deletions between pTa and pT1 tumors supports a relevant biological distinction between pTa and pT1 tumors.     

Quantitative trait locus for reading disability on chromosome 6p is pleiotropic for attention‐deficit/hyperactivity disorder

Comorbidity is pervasive among both adult and child psychiatric disorders; however, the etiological mechanisms underlying the majority of comorbidities are unknown. This study used genetic linkage analysis to assess the etiology of comorbidity between reading disability (RD) and attention‐deficit hyperactivity disorder (ADHD), two common childhood disorders that frequently co‐occur. Sibling pairs (N = 85) were ascertained initially because at least one individual in each pair exhibited a history of reading difficulties. Univariate linkage analyses in sibling pairs selected for ADHD from within this RD‐ascertained sample suggested that a quantitative trait locus (QTL) on chromosome 6p is a susceptibility locus for ADHD. Because this QTL is in the same region as a well‐replicated QTL for reading disability, subsequent bivariate analyses were conducted to test if this QTL contributed to comorbidity between the two disorders. Analyses of data from sib pairs selected for reading deficits revealed suggestive bivariate linkage for ADHD and three measures of reading difficulty, indicating that comorbidity between RD and ADHD may be due at least in part to pleiotropic effects of a QTL on chromosome 6p. © 2002 Wiley‐Liss, Inc.