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Biomedical subjects

C Rosenberg

Publications and source records attributed to C Rosenberg.

At least 73 records · Page 4Linked to original sources

Are in-patient depressives more often of the melancholic subtype? Danish University Antidepressant Group.

In contrast to out-patients, hospitalized depressed patients have been reported to respond better to tricyclic antidepressants (TCAs) than to selective serotonin reuptake inhibitors (SSRIs) and moclobemide. This may be due to differences in the type of patients included in the trials. The hypothesis that hospitalized depressed patients have a different symptom profile to out-patients was tested by comparing 352 patients from three in-patient studies with 581 patients from three out-patient studies conducted in Denmark during the period 1980-1992. All patients had major depression and were evaluated using the Hamilton Depression Scale. The full version of the Newcastle Diagnostic Rating Scale (1965) was applied to 443 of the patients. In-patients were characterized by higher scores on the items 'depressed mood', 'suicidal impulses', 'work and interest (reduced)', 'retardation', 'distinct quality of depression', 'weight loss', 'feeling of guilt' and 'nihilistic delusions', and by lower scores on the items 'somatic complaints', 'hypochondriasis', 'psychological stressors' and 'anxiety'. In total, 76% of the in-patients and 40% of the out-patients had melancholic/endogenous depression. These findings may explain why TCAs are superior to SSRIs and moclobemide in hospitalized patients, since other data indicate that TCAs seem to be the most effective treatment for the melancholic/endogenous subtype.

Ambulatory Care↗

Improvement of mild sleep-disordered breathing with CPAP compared with conservative therapy.

The aim of this randomized controlled trial was to assess the effects of treatment with continuous positive airway pressure versus conservative therapy (CT) on well-being, mood, and functional status in subjects with mild sleep-disordered breathing (SDB). One hundred and eleven subjects, aged 25 to 65 yr, with a respiratory disturbance index (RDI) of 5 to 30 and without subjective pathologic sleepiness, were randomized to nasal CPAP or to CT. Ninety-seven subjects were followed-up after 8 wk. Treatment response was assessed from changes between baseline and follow-up measures of mood, energy/fatigue, and functional status/general health. Of the 51 subjects randomized to CPAP, 25 (49%) experienced an improved outcome, as compared with 12 of 46 of subjects (26%) randomized to CT (p < 0.05). The odds of experiencing a treatment response in the CPAP as compared with the CT group were 2.72 (OR: 1.18 to 6.58, 95% CI). A beneficial effect of CPAP over CT was most evident among individuals without sinus problems and among subjects with hypertension or diabetes. Differential treatment responses were not related to degree of baseline sleepiness or SDB. This suggests that middle-aged snorers with relatively low levels of SDB (RDI < 30) may benefit more from nasal CPAP than from less specific therapy directed at improving breathing during sleep. CPAP therapy may be beneficial to a broader group of subjects than previously appreciated.

Activities of Daily Living↗

Promoting skin cancer prevention counseling by pharmacists.

OBJECTIVES: This study evaluated the effects of an intervention on rates of skin cancer prevention counseling by pharmacists. METHODS: Fifty-four pharmacies were randomly assigned to intervention or control conditions. Intervention consisted of training, feedback, and prompts. Counseling rates before and after the intervention were obtained from study confederates. RESULTS: At pretest, the proportions of control and intervention sites providing counseling at least once were 7.4% and 0%, respectively (NS). At posttest, these proportions were 3.7% and 66.7%, respectively (P < .001). CONCLUSIONS: The results indicated that the intervention was successful and that pharmacists can play an important role in educating the public about skin cancer prevention strategies.

Counseling↗

Chromosomal constitution of human spermatocytic seminomas: comparative genomic hybridization supported by conventional and interphase cytogenetics.

No data on the chromosomal constitution of spermatocytic seminomas are available thus far because of their rarity. Ploidy analysis performed on paraffin-embedded cases showed varying results from (near-) diploid to aneuploid. We applied comparative genomic hybridization on four snap-frozen primary spermatocytic seminomas of three different patients. Conventional cytogenetic analysis was successful in one, and "interphase cytogenetics" with centromeric region-specific probes was applied to another. The results from comparative genomic hybridization showed almost exclusively numerical chromosomal aberrations, in agreement with the data from karyotyping. Despite the limited number of cases studied, a nonrandom pattern of chromosome imbalances was detected: chromosome 9 was gained in all spermatocytic seminomas. This suggests that that this aberration plays a role in the development of this cancer. Interphase cytogenetics shows that the copy number of most chromosomes ranges from two to four, with an average of near trisomic. This constitutes the first report on the chromosomal constitution of spermatocytic seminomas.

Aneuploidy↗

Comparative genomic hybridization in hypotriploid/hyperdiploid tumors.

Hypotriploidy/hyperdiploidy ("intermediate ploidy") often occurs in testicular germ cell tumors of adolescents and adults. Disomic and trisomic chromosomes represent significant parts of the tumor genome and a few chromosomes fall outside the two- to three-copy number range. We performed comparative genomic hybridization (CGH) with DNA isolated from a cell line from a case of testicular germ cell tumor of adolescents and adults and found most of the ratio values to be dislocated from the baseline 1.0 and placed adjacent of the diagnostic thresholds of 0.8 and 1.2. We attributed that to the fact that, in current software packages for analysis of CGH, the fluorescence ratio baseline is assumed to correspond to the copy number of most loci of the genome. We then evaluated, instead of the commonly used fluorescent ratio value from the whole metaphase, the use of the fluorescence ratios of single chromosomes. The results permitted a clear distinction between the chromosomes with two and three copies and, in particular, of the regions deleted or amplified outside the two- to three-copy range. We concluded that the evaluation of unbalances of DNA copy number in intermediate ploidy cases is best carried out using multiple normalization.

Adolescent↗

Cytogenetic effects of softwood kraft pulp bleaching effluents and methanesulfonyl chloride in Chinese hamster ovary cells.

The genotoxicity of effluents collected from a conventional 5-stage softwood kraft pulp bleaching process was studied in Chinese hamster ovary (CHO) cells in vitro. Spent liquor from the first chlorination stage (C/D), where elemental chlorine and chlorine dioxide had been used in equal proportions, was shown to induce a dose-dependent increase in sister chromatid exchanges (SCEs) without metabolic activation (4-h treatment), with a maximum increase of 1.6 times over the control level at 204 microliters/ml; this dose also induced 15.5- and 20.5-fold increases in cells with chromatid-type chromosomal aberrations after 4-h and a 20-h treatment, respectively. Another C/D stage spent liquor from a process where the ratio of elemental chlorine and chlorine dioxide had been 9:1 produced a 40.5-fold elevation of cells with chromatid-type aberrations at 204 microliters/ml (20-h treatment). This sample clearly increased chromosomal aberrations also when tested as a concentrate (4-h treatment), which showed that the observed clastogenicity was not unspecifically due to the relatively large volumes used in the treatments with the unconcentrated liquors. In general, the use of rat liver S9 mix reduced the genotoxicity of the spent liquors. The results agree with earlier findings on the Salmonella mutagenicity of the same C/D samples: both the prokaryotic and eukaryotic assays showed a reduction in genotoxicity when the amount of elemental chlorine in the bleaching process was reduced. An effluent sample collected from the alkaline stage of the process was not clastogenic with or without metabolic activation. Methanesulfonyl chloride, a new compound identified in bleaching plant air, was found to be induce chromosomal aberrations in the presence of S9 mix.

Animals↗

RB1 deletion in gonadoblastoma in an XY female.

Cytogenetic studies of normal and tumor cells in a patient with gonadal dysgenesis and bilateral gonadoblastoma were performed. The karyotype was 46,XY in peripheral blood lymphocytes and skin fibroblasts. The conserved region of the SRY gene was detected by polymerase chain reaction amplification. Sequencing of this region did not reveal any alterations. A 46,XY chromosome constitution was observed in the right gonadoblastoma, but a partial deletion of chromosome 13 was present in the left tumor. This deletion included band 13q14, where the retinoblastoma gene is mapped. The study of the polymorphism of the variable number of tandem repeats region in intron 17 of the RB1 locus disclosed loss of heterozygosity in both the left tumor, which showed the deletion of chromosome 13, and in the right tumor, where no chromosome alterations of chromosome 13 were detected. In situ hybridization covering 130 kb of RB1 showed that a partial deletion of one of the RB1 alleles had occurred in the right tumor. Since the deletions affected different alleles in each tumor, independent events must have been involved in the development of the tumors. These findings point toward a significant role of RB1 in the development of gonadoblastoma.

Adolescent↗

Skin cancer prevention education: a national survey of YMCAs.

High skin cancer incidence and mortality rates have created a need for skin cancer prevention education. Children are an important target for this education, as overexposure to sun and sunburns at an early age have been linked to the development of skin cancer. This study identified the prevalence of skin cancer prevention education and the need for this education at YMCA swim classes. This study also assessed the feasibility of implementing Project SUNWISE, an existing skin cancer prevention curriculum, developed for YMCA swim classes. A 51-item survey was mailed to Aquatics Directors at all YMCAs with outdoor pools. Based on a 63% response rate (N = 208), only 28% of YMCAs thought the children in their swim classes were adequately protected from the sun, and only 28% offered skin protection or sun safety education in swim classes. Only 50% of YMCAs trained their swim instructors on skin cancer prevention. While 91% of YMCAs had one or more sun protection items near the pool (e.g., sunscreen, umbrella, covered area), 93% of YMCAs saw the need for additional protection. The majority of YMCAs (95%) were willing to incorporate a skin cancer prevention education curriculum, similar to Project SUNWISE, into their swim classes. This study emphasized the need for more skin cancer prevention education programs targeting children and examined the correlates of skin cancer prevention education at YMCAs. Geographic region, percent of possible sunshine, and ultraviolet radiation were significantly associated with the skin cancer prevention education program status at the YMCAs.

Administrative Personnel↗

Characteristic pattern of chromosomal gains and losses in marginal zone B cell lymphoma detected by comparative genomic hybridization.

Marginal zone B cell lymphoma (MZBCL) represents a distinct subtype of B cell non-Hodgkin's lymphoma, which has been recently recognized and defined as a disease entity. We investigated 25 cases (18 at primary diagnosis and seven during the course of disease) of MZBCL by comparative genomic hybridization (CGH) and compared these results with cytogenetic, fluorescence in situ hybridization (FISH), and Southern blot data. Twenty of the 25 cases (80%) showed gains (total 49) or losses (total 15) of genetic material. In extranodal, nodal, and splenic MZBCL, material of chromosomes 3 (52% of cases), 18 (32%), X (24%), and 1q (16%) was most frequently gained, whereas losses predominantly involved chromosomes 17 (16%) and 9 (12%). High-level amplifications involving the regions 18q21-23 and 18q21-22, respectively, were detected in two cases. Gains of chromosomes 1q and 8q and losses of chromosome 17 or 17p occurred more frequently in relapsed or progressive lymphomas. For all of the frequently affected chromosomes, CGH allowed narrowing of the relevant subregions including 3q21-23, 3q25-29 and 18q21-23. By Southern blot analysis, the BCL2, BCL6, and CMYC proto-oncogenes were found to be a part of the over-represented regions in two cases, one case, and two cases, respectively, with gains involving 18q, 3q or 8q. In 13 cases, CGH revealed chromosomal imbalances which were not detected by cytogenetic analysis but could be confirmed by FISH or Southern blot analysis in all cases investigated. On the other hand, CGH failed to detect trisomy 3, trisomy 18, and deletion 7q in three cases with a low proportion of tumor cells bearing these abnormalities, as shown by interphase FISH. The characteristic pattern of chromosomal gains and losses detected in this study confirms the distinct nature of MZBCL and may point to chromosomal regions involved in the pathogenesis of these neoplasms.

Adult↗

Neuropsychological function in mild sleep-disordered breathing.

Although a broad range of neuropsychological deficits has been reported in patients with severe sleep disordered breathing (SDB), little is known about the impact of mild SDB on neuropsychological performance. In this study, we compared neuropsychological test performance in two groups of carefully screened volunteers who differed clearly according to the respiratory disturbance index (RDI). Controls (n = 20) were identified on the basis of an RDI < 5; cases (n = 32) had an RDI in the range of 10-30. Cases and controls were well matched with regard to IQ, age, and sex. Cases had significantly more self-reported snorting and apneas and a higher body mass index than controls but did not differ according to sleepiness as measured by either the multiple sleep latency test or the Epworth sleepiness scale. An extensive battery of neuropsychological and performance tests was administered after an overnight sleep study. Cases performed significantly more poorly on a visual vigilance task (perceptual sensitivity, d': 2.24 +/- 0.64 vs. 2.70 +/- 0.53, p = 0.01, for cases and controls, respectively) and a test of working memory, the Wechsler adult intelligence scale-revised digits backwards test (6.12 +/- 2.20 vs. 7.55 +/- 2.22, p = 0.02), than controls. The groups did not differ in their performance on other tests of memory, information processing, and executive functioning. In summary, subjects with mild SDB may manifest a vigilance deficit in the absence of substantial sleepiness. Subjects with a mildly elevated RDI (10-30) without sleepiness do not appear to suffer appreciable deficits in more complex neuropsychological processes (e.g. executive functions).

Cognition Disorders↗

Effects of menopause and nasal occlusion on breathing during sleep.

Prevalence of sleep-disordered breathing (SDB) is reported to increase in menopausal women. We examined response to a nocturnal respiratory challenge (nasal occlusion) during overnight polysomnography in 31 women (45 to 55 yr). Thirteen were premenopausal, four perimenopausal, and 14 postmenopausal by history and hormonal assay. Nasal occlusion increased the apnea hypopnea index (AHI) (occlusion mean = 6.6 +/- 8.0 versus baseline mean = 1.6 +/- 2.6, p < 0.01) and arousal index (occlusion mean = 35.1 +/- 20.1 versus baseline mean = 20.7 +/- 11.6, p < 0.001), but did not change the oxygen saturation nadir in those with respiratory events (occlusion mean = 91.8 +/- 4.2 versus baseline mean = 92.0 +/- 11.6). Menopausal groups did not differ on AHI, arousal index, or oxygen saturation nadir in either condition. Key variables were compared between occlusion responders (n = 11) and nonresponders (n = 20). Responders and nonresponders were not distinguished by age, menopausal status, nor several cephalometric or anthropometric variables. Body mass index (31.1 +/- 8.5 versus 24.3 +/- 3.4, p < 0.003), neck circumference (34.0 +/- 2.5 versus 32.5 +/- 1.7 cm, p < 0.05), and mandibular-hyoid distance (18.5 +/- 3.8 versus 14.5 +/- 5.7 mm, p < 0.05) were greater in responders. These findings suggest hormonal factors may be less important than weight and facial morphology in midlife development of SDB in women.

Anthropometry↗

Interphase cytogenetics of prostatic tumor progression: specific chromosomal abnormalities are involved in metastasis to the bone.

Only limited data are available on chromosomes specifically involved in the multistep tumorigenesis of prostate cancer. To investigate the cytogenetic status at different stages of prostatic tumor development, we have applied interphase in situ hybridization (ISH) with a set of (peri) centromeric DNA probes--specific for chromosomes 1, 7, 8, and Y--to routinely processed tissue sections of prostatic specimens from 75 different individuals. Our panel consisted of: 16 normal/benign prostatic hyperplasia specimens; 23 primary, localized, prostatic tumors (N0M0 stage); 20 regional lymph node metastases (M0 stage); and 16 distant metastases. Numerical aberrations of at least one chromosome were not observed in normal/benign prostatic hyperplasia cases, but were present in localized tumors (39%), regional lymph node metastases (40%), and distant metastases (69%). Within the different pTNM groups, we observed the following aberrations (listed, within each series, in decreasing order of frequency): -Y, +8, -8, +7 in primary tumors; +8, +7, -Y, +Y, -8 in regional lymph node metastases; and +8, +7, +1, -Y, -8 in distant metastases. In primary tumors, the number of aberrant cases increased significantly with local tumor stage (p < 0.05). A significant increase in gain of chromosome 8 was also observed (p < 0.02). Gain of chromosome 7 and/or 8 showed a significant increase with progression of local tumor stage (p < 0.02). Specific involvement of chromosome 8 was seen in bone metastases, but not in hematogenous metastases to other sites (p = 0.02). Comparative genomic hybridization analysis of these bone metastases disclosed centromere 8 gains as amplifications of the (whole) 8q arm, whereas centromeric loss appeared to be due to loss of 8p sequences. With progression toward metastatic disease, an accumulation of genetic changes was seen as exemplified by gain of chromosome 1, which was solely observed in distant metastases. With tumor progression, gain of chromosomes 7 and/or 8 significantly increased (p = 0.03), whereas the number of cases with aberrations of the Y chromosome did not change. Furthermore, ploidy status determined by ISH revealed a significant increase in the number of aneuploid cases along with advancement of pTNM stage (p = 0.04). Collectively, the data strongly suggest that: (a) gain of chromosome 7 and/or 8 sequences is implicated in prostatic tumor progression; (b) gain of chromosome 8 sequences is related to local tumor growth; (c) overrepresentation of 8q sequences, most likely by isochromosome 8q formation, is involved in metastatic spread to the bone; and (d) changes in the centromeric copy number, as detected by interphase ISH, might in some cases represent structural alterations, such as an isochromosome.

Aged↗

Exon shuffling and the origin of the mitochondrial targeting function in plant cytochrome c1 precursor.

Since most of the examples of "exon shuffling" are between vertebrate genes, the view is often expressed that exon shuffling is limited to the evolutionarily recent lineage of vertebrates. Although exon shuffling in plants has been inferred from the analysis of intron phases of plant genes [Long, M., Rosenberg, C. & Gilbert, W. (1995) Proc. Natl. Acad. Sci. USA 92, 12495-12499] and from the comparison of two functionally unknown sunflower genes [Domon, C. & Steinmetz, A. (1994) Mol. Gen. Genet. 244, 312-317], clear cases of exon shuffling in plant genes remain to be uncovered. Here, we report an example of exon shuffling in two important nucleus-encoded plant genes: cytosolic glyceraldehyde-3-phosphate dehydrogenase (cytosolic GAPDH or GapC) and cytochrome c1 precursor. The intron-exon structures of the shuffled region indicate that the shuffling event took place at the DNA sequence level. In this case, we can establish a donor-recipient relationship for the exon shuffling. Three amino terminal exons of GapC have been donated to cytochrome c1, where, in a new protein environment, they serve as a source of the mitochondrial targeting function. This finding throws light upon an old important but unsolved question in gene evolution: the origin of presequences or transit peptides that generally exist in nucleus-encoded organelle genes.

Amino Acid Sequence↗

Specificity, sensitivity, and predictive value of apolipoprotein-E genotyping for sporadic Alzheimer's disease.

BACKGROUND: We aimed to determine the specificity, sensitivity, and predictive value of apolipoprotein E (APOE) genotyping in 67 consecutive patients with clinical diagnoses of sporadic Alzheimer's disease (AD) who underwent necropsy. METHODS: We studied patients who attended the Duke Memory Disorders Clinic and were diagnosed as having probable AD. These patients were followed up until they died. APOE genotyping was done during life in most cases, but in some brain tissue obtained at necropsy was used. Members of known AD families were excluded. FINDINGS: After neuropathological examination 57 (85%) of 67 of our patients were confirmed as having AD including all 43 who had at least one APOE-epsilon 4 allele. None of the patients found not to have AD carried an epsilon 4 allele. In this series, the specificity of the epsilon 4 allele was 100%, the sensitivity 75%, the positive predictive value 100%, and the negative predictive value 42%. In this necropsy-confirmed series, the epsilon 4/epsilon 4 genotype predicted AD with 100% accuracy. The epsilon 3/epsilon 4 and epsilon 2/epsilon 4 genotypes were also unexpectedly highly specific for AD. INTERPRETATION: Data from hundreds of necropsy-confirmed non-AD patients in other longitudinal necropsy series will allow the predictive value of APOE genotypes to be assessed with useful confidence limits.

Alleles↗

Cephalometric assessment in obstructive sleep apnea.

It is reported that some specific craniofacial characteristics are associated with obstructive sleep apnea syndrome (OSAS). To test this finding, the present study developed and assessed the feasibility of a craniofacial index score (CIS) in differentiating patients with OSAS from habitual snorers. Anthropometric measurements and lateral head radiographs were obtained on 24 male and 4 female patients with OSAS who had physician-diagnosed OSAS (respiratory disturbance index (RDI) >20), and 25 male and 5 female habitual snorers (RDI <20). Thirteen cephalometric and four anthropometric measure- ments were used in a discriminant model to construct the CIS. The model was able to correctly classify 82.1% of the OSAS group and 86.7% of the snoring group. In addition, variables that were related to the soft tissues, hyoid bone to mandibular plane, Body Mass Index, and soft palate length had the highest predictive value. These findings indicate that a CIS constructed from cephalometric and anthropometric measurements can be used to identify subjects with and without OSAS.

Anthropometry↗

The NodA proteins of Rhizobium meliloti and Rhizobium tropici specify the N-acylation of Nod factors by different fatty acids.

Rhizobia synthesize mono-N-acylated chitooligosaccharide signals, called Nod factors, that are required for the specific infection and nodulation of their legume hosts. The biosynthesis of Nod factors is under the control of nodulation (nod) genes, including the nodABC genes present in all rhizobial species. The N-acyl substitution can vary between species and can play a role in host specificity. In Rhizobium meliloti, an alfalfa symbiont, the acyl chain is a C16 unsaturated or a (omega-1) hydroxylated fatty acid, whereas in Rhizobium tropici, a bean symbiont, it is vaccenic acid (C18:1). We constructed R. meliloti derivatives having a non-polar deletion of nodA, and carrying a plasmid with either the R. meliloti or the R. tropici nodA gene. The strain with the R. tropici nodA gene produced Nod factors acylated by vaccenic acid, instead of the C16 unsaturated or hydroxylated fatty acids characteristic of R. meliloti Nod factors, and infected and nodulated alfalfa with a significant delay. These results show that NodA proteins of R. meliloti and R. tropici specify the N-acylation of Nod factors by different fatty acids, and that allelic variation of the common nodA gene can contribute to the determination of host range.

Acylation↗

Relationship between sleepiness and general health status.

One commonly used instrument for evaluating general health and functional status is the medical outcomes survey short form 36 (MOS). Scores obtained from this instrument are known to vary with chronic diseases and depression. However, the degree to which these health dimensions may be influenced by sleep quality or sleepiness is not well understood. A cross-sectional study was performed on the association between general health status, as determined by the MOS, with sleepiness, assessed using a standardized questionnaire [the Epworth sleepiness scale (ESS)] and the multiple sleep latency test (MSLT). One hundred twenty-nine subjects (68 women), aged 25-65 years, without severe chronic medical or psychiatric illnesses, underwent an overnight sleep study, followed by an MSLT (consisting of a series of four attempts at napping at 2-hour intervals), and completed the MOS and the ESS. The mean MSLT score was 11 +/- 2 minutes, (range 2-20) and the mean ESS score was 10 +/- 5 (range 0-24). Scores for the MOS dimensions "general health perceptions", "energy/fatigue", and "role limitations due to emotional problems" were correlated significantly with ESS scores (r = -0.30, -0.41, and -0.30, respectively; p values were all < 0.001). The MSLT was also significantly correlated with "energy/fatigue" (r = -0.19; p < 0.05). After considering the effects of chronic illness and/or body mass index in a multiple hierarchical regression analysis, sleepiness, as assessed by the ESS score, explained 8% of the variance in general health perceptions, 17% of the variance in energy/fatigue, 6% of the variance in the summary measure of well-being, and 3% of the variance in the summary measure of functional status. The variation of MOS scores with sleepiness, unrelated to age or chronic disease, suggests that measures of general health status may be broadly influenced by sleepiness and sleep quality. These data suggest that 1) sleepiness has an important impact on general health and functional status, specifically influencing self-perceptions regarding energy/fatigue; 2) a more specific assessment of sleepiness in general health evaluations may help explain some of the observed variability in these measures across subjects; and 3) general health measures may be useful in the evaluations of patients with sleep disorders.

Adult↗