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Biomedical subjects

C Rosenberg

Publications and source records attributed to C Rosenberg.

At least 19 recordsLinked to original sources

TRPC1, a human homolog of a Drosophila store-operated channel.

In many vertebrate and invertebrate cells, inositol 1,4,5-trisphospate production induces a biphasic Ca2+ signal. Mobilization of Ca2+ from internal stores drives the initial burst. The second phase, referred to as store-operated Ca2+ entry (formerly capacitative Ca2+ entry), occurs when depletion of intracellular Ca2+ pools activates a non-voltage-sensitive plasma membrane Ca2+ conductance. Despite the prevalence of store-operated Ca2+ entry, no vertebrate channel responsible for store-operated Ca2+ entry has been reported. trp (transient receptor potential), a Drosophila gene required in phototransduction, encodes the only known candidate for such a channel throughout phylogeny. In this report, we describe the molecular characterization of a human homolog of trp, TRPC1. TRPC1 (transient receptor potential channel-related protein 1) was 40% identical to Drosophila TRP over most of the protein and lacked the charged residues in the S4 transmembrane region proposed to be required for the voltage sensor in many voltage-gated ion channels. TRPC1 was expressed at the highest levels in the fetal brain and in the adult heart, brain, testis, and ovaries. Evidence is also presented that TRPC1 represents the archetype of a family of related human proteins.

Adult

PCDD/PCDF levels in the blood of workers at a pulp and paper mill.

Blood samples from 34 workers at a pulp and paper mill and from 14 control persons were analysed for 2,3,7,8-substituted PCDDs and PCDFs. There were no statistically significant differences in total lipid-adjusted PCDD/PCDF concentrations, expressed as toxic equivalents, in blood plasma between the potentially exposed bleaching plant or paper mill workers and the controls. The mean level was 61 pg/g I-TEQ in bleaching plant workers, 60 pg/g I-TEQ in paper mill workers and 49 I-TEQ pg/g in controls. Regarding the concentrations of individual isomers, however, there was an indication that the blood plasma concentrations might be affected by the living and working environment.

Adult

Selection of adrenal tumor cells in culture demonstrated by interphase cytogenetics.

Solid tumors often consist of an admixture of cell populations with different genome constitutions. Karyotyping of this material is complicated by the low mitotic index. Even when chromosome studies are feasible, altered representation of the original cell populations after cell cultivation is possible. We report a human adrenal carcinoma that exhibited a normal karyotype after cultivation but was shown to be highly aneuploid when investigated by fluorescence in situ hybridization (FISH) in direct preparations of uncultured cells with six different centromeric probes. The high frequencies of trisomy for the investigated chromosomes in these interphase cells indicate that most of the tumor cells were in the triploid range. Strong selection for disomic cells was detected in interphase preparations after one and two subcultures and was even stronger in the corresponding metaphase preparations. Trisomy for chromosome 15 appeared to be maintained independent of triploidy and might play a role in cultured cell survival. The number of chromosome 17 centromeres was not increased in polyploid cells, suggesting loss of this chromosome in the original cells of the tumor.

Adrenal Gland Neoplasms

High resolution DNA fiber-fish on yeast artificial chromosomes: direct visualization of DNA replication.

Fluorescent in situ hybridization (FISH) is a powerful, direct and sensitive technique with a wide resolution range that enables the simultaneous study of multiple targets, labelled in different colours. Spreading techniques, denoted here as 'Fiber-FISH', increase FISH-resolution to the DNA fiber, using decondensed nuclear DNA as hybridization target. FISH could be a powerful analytical tool for thorough physical examination of yeast artificial chromosomes (YACs) which are often chimaeric or contain internal deletions. However, with one exception restricted to meiotic yeast chromosomes, FISH has not been used successfully on yeast/YAC DNA. We have developed a fast and simple method that can be applied routinely for compositional and structural analysis of cosmid and YAC DNA in yeast. It enables precise localization and ordering of clones, resolves overlaps and distances and gives a detailed picture of the integrity and colinearity of both probe and target. The combination of high resolution, signal abundance and short yeast cell cycle allows direct visualization of replicating DNA fibers. In a 400 kb region of the human dystrophin gene, we identified two replication origins, demonstrating that human DNA cloned in yeast is capable of initiating its own replication.

Chromosomes, Artificial, Yeast

Gas chromatographic-mass spectrometric determination of chlorophenols in the urine of sawmill workers with past use of chlorophenol-containing anti-stain agents.

The aim of this work was to establish whether workers at sawmills where chlorophenol-containing anti-stain agents had been previously used were still exposed to chlorophenols. A gas chromatographic-mass spectrometric (GC-MS) procedure for the determination of chlorophenols in urine was developed. Chlorophenols were determined from hydrolysed urine as acetylated derivatives and determined by GC-MS using selected ion monitoring (SIM). Isolation of the chlorophenols with toluene gave the best extraction efficiencies (65-119%). Stability tests at -20 degrees C showed no degradation of the chlorophenols studied during 6 months. The limit of quantification was 3.6 ng mg-1 creatinine for 2,4,6-trichlorophenol, 5.5 ng mg-1 for 2,3,4,6-tetrachlorophenol and 3.6 ng mg-1 for pentachlorophenol. Traces of 2,4,6-trichlorophenol, 2,3,4,6-tetrachlorophenol and pentachlorophenol were found both in previously exposed workers and in non-exposed controls, the urinary concentrations ranging from 1.1 to 15.9 ng mg-1 creatinine. The concentrations of urinary chlorophenols in previously exposed workers were of the same magnitude as those found in non-exposed controls and in the general population. The results show that it is unlikely that sawmill workers would be currently occupationally exposed to chlorophenols or polychlorinated dibenzo-p-dioxins and dibenzofurans via a contaminated work environment.

Acetylation

The effect of zidovudine and 2'3'-dideoxyinosine on human trophoblast in culture.

Trophoblast from term and first trimester placenta, maintained in culture, were exposed to 20 mumoles/l zidovudine or 2'3'dideoxyinosine. Several indices of function were measured and compared to control trophoblast in parallel culture. The results from individual placentas were examined by Student's t-test and cumulative results by ANOVA. Neither zidovudine or 2'3'-dideoxyinosine had statistically significant effects on the function of term trophoblast, following a 48 hr exposure to the drug as indicated by hCG secretion, protein synthesis and glucose consumption. In one of five placentas exposed to zidovudine, progesterone secretion was reduced as compared to its control but remained in the high range. Zidovudine had no significant effect on cultured trophoblast isolated from first trimester placenta even after prolonged exposure to the drug for eleven days. Both term and first trimester trophoblast in culture tolerate prolonged exposure to high concentrations of zidovudine or 2'3'-dideoxyinosine. Human trophoblast in culture provides a safe in vitro model for the screening of drugs intended for use during pregnancy.

Analysis of Variance

Judgments of azimuth and elevation as a function of monoscopic and binocular depth cues using a perspective display.

The purpose of this study was to investigate the use of three-dimensional display formats for judgments of spatial information using an exocentric frame of reference. Eight subjects judged the azimuth and elevation that separated two computer-generated objects using either a perspective or stereoscopic display. Errors, which consisted of the difference in absolute value between the estimated and actual azimuth or elevation, were analyzed as the response variable. The data indicated that the stereoscopic display resulted in more accurate estimates of elevation, especially for images aligned approximately orthogonally to the viewing vector. However, estimates of relative azimuth direction were not improved by use of the stereoscopic display. Furthermore, it was shown that the effect of compression resulting from a 45-deg computer graphics eye point elevation produced a response bias that was symmetrical around the horizontal plane of the reference cube, and that the depth cue of binocular disparity provided by the stereoscopic display reduced the magnitude of the compression errors. Implications of the results for the design of spatial displays are discussed.

Adult

Visual loss in pregnant women with pituitary adenomas.

OBJECTIVE: To investigate the potential risk for developing visual loss during single or multiple pregnancies in women with pituitary adenomas. DESIGN: Cohort study. SETTING: Referral center of a neuro-ophthalmology service. PATIENTS: 65 consecutive women with pituitary adenomas who had not been previously treated with surgery or radiation were monitored during 111 pregnancies. Sixty had increased levels of serum prolactin or growth hormone and 5 did not. MAIN OUTCOME MEASURES: Visual field or acuity loss was compared with the baseline size of the adenoma measured on the coronal view of the computed tomographic or magnetic resonance image. RESULTS: Computed tomography or magnetic resonance imaging showed a definitive tumor (> 0.3 cm, vertical height) in 57 patients, 8 of whom had macroadenomas (> or = 1.1 cm). Visual field loss occurred in 6 of 8 primiparous patients, all with adenomas greater than 1.1 cm (range, 1.2 to 2.5 cm). None of the 57 patients (95% CI, 0% to 6.3%) with a microadenoma or presumed microadenoma of 1 cm or smaller developed visual loss after as many as four full-term pregnancies. CONCLUSIONS: The risk for developing visual loss during single or multiple pregnancies in patients with microadenomas was small. Six of eight pregnant women with macroadenomas, however, developed visual field loss during pregnancy.

Acromegaly

Genetic alterations of chromosome 17 in human breast carcinoma studied by fluorescence in situ hybridization and molecular DNA techniques.

Fluorescence in situ hybridization (FISH) with a chromosome 17 centromere-specific probe was used together with Southern blot analyses and PCR amplification of a polymorphic segment to characterize 13 breast carcinomas. Cells with an abnormal number of chromosome 17 centromeres were found mixed with disomic cells in nine of the 13 tumors studied. Three of the four cases found to have a normal number of chromosome 17 centromeres had DNA alterations restricted to allelic imbalance of the two most distal markers on 17p; the fourth had no detectable alterations. In contrast, of the seven tumors found to have genetic alterations elsewhere on chromosome 17, all had more than one cell population when examined for numerical chromosome 17 alterations. The present data support the hypothesis that alterations at the distal short arm of chromosome 17 represent earlier events in the tumorigenic process than do the other chromosome 17 abnormalities observed. The results of molecular DNA studies interpreted as allelic imbalance of distal 17p markers in most cases probably reflect chromosomal rearrangements like loss of specific loci, rather than monosomies and large deletions. The report illustrates the usefulness of FISH when added to current molecular DNA techniques.

Breast Neoplasms

Increased cholecystectomy rates among Medicare patients after the introduction of laparoscopic cholecystectomy.

A study was undertaken of Medicare claims coded for cholecystectomy and those coded for laparoscopic cholecystectomy for the four year period 1990-1993 in New York State. During this time period there was a 28.12% increase in total cholecystectomies performed and an increase in the proportion of laparoscopic cholecystectomies from 15.86% to 50.0%. The increase in total cholecystectomies appears to be driven by a dramatic increase in laparoscopic procedures. Possible reasons for this increase include the performance of laparoscopy on patients previously assessed as too risky to undergo the conventional procedure, laparoscopy on mildly symptomatic patients who had previously put off a perceived higher risk open procedure and a possible broadening of indications for gallbladder surgery. The dramatic increase in the numbers of cholecystectomies performed in the early 1990s may be due in part to procedures performed on a large pool of procrastinating mildly symptomatic patients. If this is the case, then these increased rates should decline to baseline levels as soon as this pool of patients is exhausted. However, if surgeons are performing laparoscopy on asymptomatic patients with gallstones, then these rates may well be sustained. Such a broadening of indications for gallbladder surgery is of concern to many and has prompted the issuance of guidelines concerning the treatment of gallstones. Any broadening of indications for gallbladder surgery also has significant implications for health care costs and the use of health care resources.

Aged

Antinociception without motor blockade after subarachnoid administration of S-(+)-ibuprofen in rats.

This study was designed to determine whether the nonsteroidal anti-inflammatory drug (NSAID) sodium S-(+)-ibuprofen (IB), can be used intrathecally as a substitute analgesic for opiates to avoid the side effects of intrathecal narcotics. One week or more after surgical implantation of subarachnoid catheters, four groups of Sprague-Dawley rats were given 0.05 ml subarachnoid injections containing one of the following: Group A, normal saline (NS); Group B, IB 0.25 mg, 0.5 mg and 1.5 mg; Group C, morphine (M) 0.05 mg and 0.025 mg; Group D received NS or IB 1.5 mg. Animals were sacrificed for spinal cord examination one week after injection. Tail flick response latency (TFL) was determined before and 15, 30, 60, 120 and 180 minutes after each injection. TFL differences were compared. IB 1.5 mg vs NS, IB 0.5 mg vs NS, IB 0.25 mg vs M 0.05 mg, IB 0.25 mg vs M 0.025 mg, M 0.05 mg vs NS, and M 0.025 vs NS showed p < 0.05. IB 1.5 mg vs M 0.05 mg and M 0.025 mg, IB 0.5 mg vs M 0.05 mg and M 0.025 mg revealed no significant difference. No motor impairment was observed in any animal. Light microscopy of the spinal cord revealed no evidence of pathological changes in any animal (group D).

Analysis of Variance

Genotoxicity of kraft pulp spent liquors from different types of chlorination procedures.

The genotoxicity of spent liquors from kraft softwood and hardwood pulp bleaching processes was studied using the Ames Salmonella test and the SOS chromotest. The induction of micronuclei, in vivo, was assayed in bone marrow erythrocytes of B6 mice treated with softwood first chlorination stage spent liquor. The softwood bleaching process used a combination of Cl2 and ClO2 at the first chlorination stage. During the study the amount of free chlorine at the first chlorination stage in the softwood bleachery was gradually decreased, although the amount of active chlorine remained the same. Enzymatic bleaching was also used in a softwood process together with chlorine (Cl2 + ClO2). The hardwood bleaching plant used only ClO2 at the first chlorination stage. A decrease in genotoxicity, corresponding to the decrease in Cl2, was observed in the Ames Salmonella assays of the softwood bleaching plant effluents. A similar decrease was observed in the SOS chromotest. The highest decrease in mutagenic activity was observed when enzymatic bleaching was used together with chlorine.

Animals

Citalopram and imipramine in the treatment of depressive patients in general practice. A Nordic multicentre clinical study.

Two dose levels of citalopram, 10-30 mg and 20-60 mg, were compared with imipramine, 50-150 mg, in depressed patients treated in general practice. This was a multicentre study carried out in Denmark, Sweden, Norway, and Finland. The duration of treatment was 6 weeks with an optional continuation phase of a further 16 weeks. The patients were assessed by means of the Hamilton Rating Scale for Depression (HAMD), Clinical Global Impressions (CGI), and a visual analogue self-rating scale for depression. Observed and spontaneously reported adverse events were recorded. A total of 472 patients were entered into the study and 400 patients completed the 6 week trial period. A total of 297 patients completed the optional 22 week double-blind period. A clear reduction of the HAMD total scores was seen in all three treatment groups with no significant differences between groups. A reduction of the HAMD anxiety factor and sleep factor scores was also seen with no significant differences between treatments. The imipramine-treated patients showed a higher frequency of adverse events, especially the anticholinergic type, than citalopram-treated patients. Most patients entered into the continuation phase remained well.

Adolescent

The effects of topical hypothermia and steroids on ATP levels in an in vivo liver ischemia model.

Complex hepatic surgery often requires occlusion of the portal triad in order to decrease parenchymal bleeding. This study was undertaken to evaluate the effects of topical hypothermia and intravenous steroids on liver ischemia by measuring adenosine triphosphate (ATP) levels within the hepatic parenchyma. Forty New Zealand white rabbits were divided into four experimental and four control groups. All experimental animals underwent laparotomy and ligation of the porta hepatis. Serial liver biopsy specimens were obtained at predetermined time intervals. Group I received no further intervention. Group II were topically cooled until intrahepatic temperature reached 30 degrees C. Group III received preligation intravenous methylprednisolone (30 mg/kg). Group IV received both steroids and topical hypothermia. The corresponding control groups underwent laparotomy and isolation of the porta without ligation. Adenosine triphosphate was extracted from the liver parenchyma and quantified by high-performance liquid chromatography (HPLC). The data were analyzed using a three-factor mixed analysis of variance (ANOVA). There was a statistically significant protective effect on ATP levels provided by topical hypothermia at 15 and 30 minutes of ischemia (p < 0.01), but not at 60 minutes (p > 0.05). Steroids were not found to have any protective effect on ATP levels at any time point. The combination of steroids and topical hypothermia provided significant preservation of hepatic parenchymal ATP levels, although less than that of hypothermia alone, at 15 and 30 minutes of ischemia (p < 0.01).

Adenosine Triphosphate

Assessment of the validity and utility of a sleep-symptom questionnaire.

Although questionnaires have been developed to assess symptoms of obstructive sleep apnea (OSA), their overall reliability and utility have not been established. We have evaluated the ability of a questionnaire to identify increased apnea activity (IAA) in 465 participants in an epidemiologic study of OSA. Subjects and their roommates each completed a questionnaire and underwent in-home sleep studies. Responses to 56 questions about sleep habits, sleepiness, and daytime performance were analyzed with factor analysis, logistic regression, and receiver-operator curves (ROCs). Factor analysis demonstrated that 16 questions, grouped into five factors (functional impact of sleepiness, self-reported breathing disturbances, roommate-observed breathing disturbances, driving impairment, and insomnia) explained 67% of the variance in the questionnaire data. Symptom questions demonstrated internal consistency (Cronbach correlations: 0.91 to 0.98). Moderate levels of agreement were observed between self- and roommate-reported responses for nine of ten questions asked of both the subject and his/her partner (kappa statistics: 0.34 to 0.57). Logistic regression analysis demonstrated that IAA could be best predicted by three questions about intensity of snoring, roommate-observed choking, and having fallen asleep while driving (ROC area: 0.78). Use of symptoms with data on gender and body mass index (BMI) improved predictive ability by 10% (ROC area: 0.87). Thus, questionnaire data provide a valid means of characterizing symptom distributions in population surveys of OSA. Predictive ability is not significantly improved with multiple questions or a separate roommate questionnaire, but is improved with consideration of data on BMI and gender.

Adult

Chronic pain in a geographically defined general population: studies of differences in age, gender, social class, and pain localization.

OBJECTIVE: To establish basic epidemiological data on chronic pain (duration > 3 months) in a defined population. Relationships between age, gender, and social class were tested. DESIGN: A survey of pain symptoms, including location, intensity, duration, and functional capacity, was conducted by means of a mail questionnaire. SETTING: General populations in two Swedish primary health care districts. Medical care was provided in a state health system. SUBJECTS: A random sample (from the population register) of 15% of the population aged 25-74 (n = 1,806). The response rate was 90%. OUTCOME MEASURES: Descriptive epidemiologic data in relation to objectives of the study. RESULTS: Without sex differences, 55% (95% confidence interval, 53-58%) of the population had perceived persistent pain for 3 months and 49% for 6 months. Among individuals with chronic pain, 90% localized their pain to the musculoskeletal system to a variable extent. Women experienced more multiple localizations of pain and had pain in the neck, shoulder, arm, and thigh to a greater extent than men. Prevalence of pain increased by age up to 50-59 years for both genders and then slowly decreased. The neck-shoulder area was the most common site of pain (30.2%), followed by the lower back (23.2%). Even in the youngest age groups more than one of four reported chronic pain. Blue-collar workers and employers (including farmers) reported chronic pain to a greater extent than other groups. In 13% of the population, manifest pain problems were associated with reduced functional capacity. CONCLUSION: Chronic pain symptoms are common but unevenly distributed in a general population. The results may influence planning and consultation in primary health care as well as warranting selective prevention activities.

Adult

Signaling and host range variation in nodulation.

Rhizobium, Bradyrhizobium, and Azorhizobium strains, collectively referred to as rhizobia, elicit on their leguminous hosts, in a specific manner, the formation of nodules in which they fix nitrogen. Rhizobial nod genes, which determine host specificity, infection, and nodulation, are involved in the exchange of low molecular weight signal molecules between the plant and the bacteria as follows. Transcription of the nod operons is under the control of NodD regulatory proteins, which are specifically activated by plant flavonoid signals. The common and species-specific structural nod genes are involved in turn in the synthesis of specific lipo-oligosaccharides that signal back to the plant to elicit root-hair deformations, cortical-cell divisions, and nodule-meristem formation.

Fabaceae