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Biomedical subjects

T Roth

Publications and source records attributed to T Roth.

At least 55 records · Page 3Linked to original sources
PubMed2000

A human REV7 homolog that interacts with the polymerase zeta catalytic subunit hREV3 and the spindle assembly checkpoint protein hMAD2.

Widespread alteration of the genomic DNA is a hallmark of tumors, and alteration of genes involved in DNA maintenance have been shown to contribute to the tumorigenic process. The DNA polymerase zeta of Saccharomyces cerevisiae is required for error-prone repair following DNA damage and consists of a complex between three proteins, scRev1, scRev3, and scRev7. Here we describe a candidate human homolog of S. cerevisiae Rev7 (hREV7), which was identified in a yeast two-hybrid screen using the human homolog of S. cerevisiae Rev3 (hREV3). The hREV7 gene product displays 23% identity and 53% similarity with scREV7, as well as 23% identity and 54% similarity with the human mitotic checkpoint protein hMAD2. hREV7 is located on human chromosome 1p36 in a region of high loss of heterozygosity in human tumors, although no alterations of hREV3 or hREV7 were found in primary human tumors or human tumor cell lines. The interaction domain between hREV3 and hREV7 was determined and suggests that hREV7 probably functions with hREV3 in the human DNA polymerase zeta complex. In addition, we have identified an interaction between hREV7 and hMAD2 but not hMAD1. While overexpression of hREV7 does not lead to cell cycle arrest, we entertain the possibility that it may act as an adapter between DNA repair and the spindle assembly checkpoint.

Amino Acid Sequence↗
PubMed2000

A five week, polysomnographic assessment of zaleplon 10 mg for the treatment of primary insomnia.

Objective: To examine the hypnotic efficacy of zaleplon 10 mg, a selective benzodiazepine receptor agonist, over a period of 35 nights in primary insomniacs.Methods: A double-blind, parallel-group, placebo-controlled design was employed. Subjects were 113 men and women, ages 18 to 65 years. Polysomnographic and subjective sleep data were collected during baseline, on two nights during each of five treatment weeks, and on the first two nights after discontinuation of active medication.Results: Sleep latency was significantly shortened with zaleplon 10 mg for all 5 weeks of treatment as assessed by polysomnography and by subjective sleep measures. Total sleep time, whether evaluated with polysomnography or with subjective estimates, was inconsistently affected. Sleep architecture was similar with zaleplon and placebo. There was no evidence of tolerance to the sleep promoting effects of zaleplon during the five weeks of administration, and there was no rebound insomnia upon discontinuation. Adverse events occurred with equal frequency in the zaleplon and placebo groups.Conclusions: Zaleplon 10 mg is effective in the treatment of sleep onset insomnia over a period of 35 nights, with minimal evidence of undesired effects.

Journal Article↗
PubMed2000

X-ray densitometry for the measurement of regional myocardial perfusion.

The evaluation of regional myocardial blood flow (RMBF) during cardiac catheterization is of particular diagnostic interest. The purpose of this investigation was to validate x-ray densitometric parameters for the evaluation of RMBF. In five anesthetized dogs, arterial flow in the circumflex coronary artery was measured continuously with an electromagnetic flowmeter, and RMBF was determined by colored microspheres. Five different perfusion levels were created by mechanical obstruction of the coronary artery or by intravenous infusion of adenosine. At each steady-state perfusion level, digital subtraction coronary angiograms were obtained for densitometric analysis. Results documented a close correlation between the related time parameters 1/Mean Transit Time (1/MTT, r2 = 0.969), and 1/Rise Time (1/RT, r2 = 0.965) and RMBF over a wide range between 0.36 ml/(min x g) and 11.16 ml/(min x g). Maximum myocardial contrast density (Imax) also showed a good, but inverse correlation (r2 = 0.889) with RMBF and, therefore, did not reflect vascular volume. Contrast medium Appearance Time (AT) showed no correlation to RMBF (r2 = 0.017). Repeat densitometric measurements for different perfusion levels revealed a good reproducibility for MTT (accuracy: 0.001 s; precision: 0.447 s or 6.7 %) and RT (accuracy: 0.014 s; precision: 0.202 s or 10.4 %), while AT (accuracy: 0.072 s; precision: 0.420 s or 68.5%) and Imax (accuracy: 0.022 GL; precision: 1.197 GL or 44.5%) showed substantial variation. Myocardial perfusion reserve (MPR) calculated from RT (r2 = 0.90) or MTT (r2 = 0.94) showed better correlations to RMBF reserve than MPR calculated from AT (r2 = 0.04). In conclusion, only 1/MTT and 1/RT showed a good reproducibility and a close correlation to RMBF. Therefore, only these parameters can be recommended for calculations of RMBF and its reserve under clinical conditions.

Absorptiometry, Photon↗
PubMed2000

[Crohn's disease of the appendix].

A giant appendix is an extremely rare and improbable finding during surgery in suspected cases of acute appendicitis. Although this condition is primarily suggestive of neoplasia, it is usually due to an inflammatory or infectious disease. We report a case of Crohn's disease limited to the appendix, which was diagnosed after a short right ileocolectomy. Only 156 similar diagnoses have been reported in the literature to date. This disease appears to have a benign course and therefore differs from classical Crohn's ileocolitis. For this reason, these patients do not require any specific investigation or follow-up.

Adult↗
PubMed2000

Diagnosis and management of insomnia.

Insomnia is a significant public health issue. Good sleep is essential for emotional and physical wellbeing. The importance of adequate sleep is evidenced by the fact that insomnia can adversely affect physical and mental health. The National Heart, Lung, and Blood Institute Working Group on Insomnia defines insomnia as an experience of inadequate or poor-quality sleep characterized by one or more of the following: difficulty falling asleep, difficulty maintaining sleep, waking up too early in the morning, or unrefreshing sleep. The symptoms of insomnia also include daytime consequences such as tiredness, lack of energy, difficulty concentrating, or irritability. Insomnia can be a symptom of an underlying medical, psychiatric, sleep, or circadian disorder or a disorder in itself (i.e., primary insomnia). This paper will present information about the prevalence, morbidity, causes, and diagnoses of insomnia, and the behavioral and pharmacologic management of this disorder.

Humans↗
PubMed2000

In vitro and in vivo efficacy of acid-sensitive transferrin and albumin doxorubicin conjugates in a human xenograft panel and in the MDA-MB-435 mamma carcinoma model.

Acid-sensitive transferrin and albumin conjugates with doxorubicin have recently been developed with the aim of circumventing the systemic toxicity and improving the therapeutic efficacy of this anticancer agent. The in vitro activity of two acid-sensitive transferrin and albumin doxorubicin conjugates and free doxorubicin was evaluated in twelve human tumour xenografts using a clonogenic assay. The inhibitory effects and the activity profile of the conjugates was, in general, comparable to that of doxorubicin (mean IC(70) -value for doxorubicin approximately 0.1 microM and 0.1 - 0.4 microM for the conjugates). Subsequently, the efficacy of an acid-sensitive transferrin and albumin doxorubicin conjugate, which both incorporated a phenylacetyl hydrazone bond as a predetermined breaking point, was evaluated in the xenograft mamma carcinoma model MDA-MB-435 in comparison to free doxorubicin (dose, i.v.: 2 x 4, 8 and 12 mg/kg). The conjugates showed significantly reduced toxicity (reduced lethality and body weight loss) with a concomitantly stable or slightly improved antitumour activity compared to free doxorubicin. At the dose of 12 mg/kg mortality was unacceptably high in the doxorubicin treated group ( approximately 80%); in contrast, no mortality was observed with the conjugate treated animals with body weight loss < 10 %. In a further experiment, therapy with the acid-sensitive doxorubicin albumin conjugate at 3 x 12 mg/kg in the MDA-MB-435 model resulted in a significantly improved antitumour activity over free doxorubicin at its optimal dose of 2 x 8 mg/kg. In conclusion, acid-sensitive transferrin and albumin doxorubicin conjugates can be administered at higher doses than free doxorubicin in nude mice models with a concomitant improvement in antitumour activity. Interestingly, there is no pronounced difference between identically constructed transferrin and albumin doxorubicin conjugates with regard to in vitro or in vivo efficacy.

Animals↗
PubMed2000

Sleep organization and regulation.

Sleep is a vital, complex state with as yet unknown functions. It is active and highly organized and is regulated by homeostatic, circadian, and ultradian processes. It consists of two distinct sleep states, rapid eye movement (REM) and non-rapid eye movement (NREM), both of which have a dramatic impact on many aspects of physiology and behavior. The significance and consequences of the REM-NREM organization of sleep are not known. On the other hand, the sleep state and its organization are quite fragile and dynamic. Any number of factors can disrupt sleep and its expression, and its nature changes over the life span. What is certain is that any reduction and/or disruption of sleep hinders an organism's ability to navigate through the waking state.

Humans↗
PubMed1999

Characteristics of insomnia in the United States: results of the 1991 National Sleep Foundation Survey. I.

The National Sleep Foundation in conjunction with the Gallup Organization conducted telephone interviews with a sample of Americans (N = 1000) to examine the prevalence and nature of difficulty with sleep. Consistent with other national studies, about one-third of Americans reported some type of sleep problem. Approximately one in four reported occasional insomnia while 9% reported that their sleep difficulty occurred on a regular nightly basis. The problem most frequently reported by insomniacs was waking up in the morning feeling drowsy or tired, followed by waking up in the middle of the night, difficulty going back to sleep after waking up and difficulty falling asleep initially. Importantly, insomniacs rarely visited a physician to discuss their sleep problem and four out of ten insomniacs self-medicated with either over-the-counter medications or with alcohol. Two-thirds of the insomniacs reported that they did not have an understanding of available treatments for insomnia.

Adolescent↗
PubMed1999

Daytime consequences and correlates of insomnia in the United States: results of the 1991 National Sleep Foundation Survey. II.

The daytime consequences and correlates of insomnia were examined in the National Sleep Foundation and the Gallup Organization survey of 1,000 randomly selected Americans. Respondents were grouped as having occasional insomnia, chronic insomnia or no insomnia. There were dramatic differences in reported waking behaviors and psychosocial measures by insomniacs compared to those who do not report sleep difficulty. These problems include impaired concentration, impaired memory, decreased ability to accomplish daily tasks and decreased enjoyment of interpersonal relationships. Importantly, most of these variables showed an increasing degree of impairment with greater frequency of sleep disturbance. These findings suggest that insomnia negatively impacts aspects of waking function related to quality of life.

Accidents, Traffic↗
PubMed1999

Psychometric evaluation of daytime sleepiness and nocturnal sleep onset scales in a representative community sample.

BACKGROUND: The public health importance of daytime sleepiness as a risk factor for accidents, interpersonal problems, and decreased productivity has been recognized. However, epidemiologic research on this topic has been limited by the reliance on laboratory measures (i.e., the Multiple Sleep Latency Test-MSLT). Two scales, daytime sleepiness and nocturnal sleep onset, have been identified from the self-report Sleep-Wake Activity Inventory (SWAI) in a clinic sample and validated against the MSLT. This study evaluates the replicability of the two scales in a population sample and assesses potential thresholds in scale scores that distinguish normal from pathologic levels of daytime sleepiness and difficulty falling asleep. METHODS: The sample consisted of 2181 subjects 18-45 years old in the Detroit metropolitan area. All sleep characteristic information covered the 2 weeks prior to interview. Split-half sample factor analyses were conducted to assess replicability of the results. Distribution of scale scores and their relation to construct validity variables were used to evaluate possible thresholds. RESULTS: A two-factor model appeared to best account for the variation among the 12 items from the SWAI. The two factors accounted for 50% of the variance in both split-half sample analyses. The revised eight-item daytime sleepiness and two-item nocturnal sleep onset scales showed good and fair internal consistency respectively across both split-half samples. There appeared to be a "natural break" in daytime sleepiness scale scores that was associated with a substantial and consistent change in number of hours slept. No breaks appeared in nocturnal sleep onset scores. CONCLUSIONS: This study replicated the results of the clinic-based study and suggested a potentially useful diagnostic threshold for self-report excessive daytime sleepiness. Epidemiology of sleep depends on the ability to move from the laboratory to population surveys in reliable and valid ways. Development of self-report is a step in that direction.

Adolescent↗
PubMed1999

The detection of brief daytime sleep episodes.

INTRODUCTION: In the present study we evaluated the characteristics of sleep-onset detection (during daytime nap opportunities) as a function of differing sleep lengths among healthy, asymptomatic subjects. METHODS: Twenty subjects were randomized into a Latin square design in which each subject received 1, 5, 10, and 20 minutes of sleep during an MSLT. Subjects were asked after each nap if they fell asleep. The rate of sleep detection was analyzed as a function of sleep duration. RESULTS: Three subjects detected sleep onset after 1 minute of sleep, 7 subjects after 5 minutes of sleep, 10 subjects after 10 minutes of sleep, and 14 after 20 minutes of sleep (chi 2 = 9.63, p < .05). CONCLUSIONS: The present data indicate the importance of sleep duration in an individual's ability to detect the occurrence of sleep. Importantly, only three subjects detected sleep after 1 minute of sleep, emphasizing the dangerous nature of brief sleep episodes in the context of public safety.

Adult↗
PubMed1999

[Giant diverticula of the colon. Apropos of 2 cases].

Giant diverticulum of the colon is a rare complication of the colonic diverticulosis. It generally involves the sigmoid colon. In the chronic form, without symptoms or with only a few non-specific symptoms, an abdominal mass is frequently palpable. A plain abdominal radiogram, showing a gas-filled cyst, can suggest the diagnosis. If needed, an abdominal CT scan is appropriate and seems to be more accurate than a barium enema. The treatment of choice is a segmental resection of the colon involving the giant diverticulum, followed by a direct anastomosis. Despite the old age of these patients, both postoperative morbidity and mortality are low and justify such a radical approach. The acute clinical presentation (about 20%) is generally due to a peritonitis by perforation of the giant diverticulum and requires an emergency colectomy.

Aged↗
PubMed1999

Ethanol as a hypnotic in insomniacs: self administration and effects on sleep and mood.

The purpose of this study was to assess the effects of low ethanol doses on sleep and mood and to assess its reinforcing effects used as a hypnotic. Twenty healthy adults, aged 21-45 yrs, all moderate social drinkers, were studied: eleven subjects had insomnia and nine were normal sleepers, as documented by clinical polysomnography. On two sampling nights each, ethanol (0.5 g/kg) or placebo was administered before sleep in color-coded cups presented in three doses (0.2, 0.2, and 0.1 g/kg) separated by 15 min. On three subsequent nights subjects chose their preferred presleep beverage (0.2 g/kg ethanol or placebo) based on cup color and were given an opportunity for 3 additional refills (0.2 g/kg each) of the chosen beverage at 15 min intervals, yielding a total possible dose of 0.8 g/kg. Insomniacs chose ethanol 67% of nights and normals 22%. Insomniacs chose significantly more ethanol refills than normals for an average nightly dose of 0.45 g/kg and normals took significantly more placebo refills. On the sampling nights 0.5 g/kg ethanol reduced REM sleep for both groups for the 8-hr sleep period and in insomniacs increased stage 3-4 sleep and reduced stage 1 sleep during the first half of the night to the level seen in the normals. Other sleep variables were not altered in either group or halves of the night. Presleep improvements in the Profile of Mood States tension and concentration factors were also associated with ethanol administration. Thus, acutely, both sleep and mood effects appear to be associated with the reinforcing effects of ethanol as a hypnotic for insomniacs.

Adult↗
PubMed1999

Acid-sensitive polyethylene glycol conjugates of doxorubicin: preparation, in vitro efficacy and intracellular distribution.

Coupling anticancer drugs to synthetic polymers is a promising approach of enhancing the antitumor efficacy and reducing the side-effects of these agents. Doxorubicin maleimide derivatives containing an amide or acid-sensitive hydrazone linker were therefore coupled to alpha-methoxy-poly(ethylene glycol)-thiopropionic acid amide (MW 20000 Da), alpha,omega-bis-thiopropionic acid amide poly(ethylene glycol) (MW 20000 Da) or alpha-tert-butoxy-poly(ethylene glycol)-thiopropionic acid amide (MW 70000 Da) and the resulting polyethylene glycol (PEG) conjugates isolated through size-exclusion chromatography. The polymer drug derivatives were designed as to release doxorubicin inside the tumor cell by acid-cleavage of the hydrazone bond after uptake of the conjugate by endocytosis. The acid-sensitive PEG conjugates containing the carboxylic hydrazone bonds exhibited in vitro activity against human BXF T24 bladder carcinoma and LXFL 529L lung cancer cells with IC70 values in the range 0.02-1.5 microm (cell culture assay: propidium iodide fluorescence or colony forming assay). In contrast, PEG doxorubicin conjugates containing an amide bond between the drug and the polymer showed no in vitro activity. Fluorescence microscopy studies in LXFL 529 lung cancer cells revealed that free doxorubicin accumulates in the cell nucleus whereas doxorubicin of the acid-sensitive PEG doxorubicin conjugates is primarily localized in the cytoplasm. Nevertheless, the acid-sensitive PEG doxorubicin conjugates retain their ability to bind to calf thymus DNA as shown by fluorescence and visible spectroscopy studies. Results regarding the effect of an acid-sensitive PEG conjugate of molecular weight 20000 in the chorioallantoic membrane (CAM) assay indicate that this conjugate is significantly less embryotoxic than free doxorubicin although antiangiogenic effects were not observed.

Animals↗