Failure to phosphorylate the retinoblastoma gene product in senescent human fibroblasts.

Heterokaryon studies suggest that senescent and quiescent human diploid fibroblasts (HDF) contain a common inhibitor of entry into S phase. DNA synthesis can be induced in senescent and quiescent HDF by fusing them with cells containing DNA viral oncogenes such as SV40 T antigen, adenovirus E1A, or human papillomavirus E7. Both senescent and quiescent HDF contained the unphosphorylated form (p110Rb) of the retinoblastoma protein, a putative inhibitor of proliferation. After serum stimulation, senescent HDF did not phosphorylate p110Rb and did not enter S phase, whereas quiescent HDF phosphorylated p110Rb and entered S phase. These findings, combined with the observations that T antigen, E1A, and E7 form complexes with, and presumably inactivate, unphosphorylated p110Rb, suggest that failure to phosphorylate p110Rb may be an immediate cause of failure to enter S phase in senescent HDF.

Levels of methyleugenol in a subset of adults in the general U.S. population as determined by high resolution mass spectrometry.

We developed a sensitive and accurate analytical method for quantifying methyleugenol (ME) in human serum. Our method uses a simple solid-phase extraction followed by a highly specific analysis using isotope dilution gas chromatography-high resolution mass spectrometry. Our method is very accurate; its limit of detection is 3.1 pg/g and its average coefficient of variation is 14% over a 200-pg/g range. We applied this method to measure serum ME concentrations in adults in the general U.S. population. ME was detected in 98% of our samples, with a mean ME concentration of 24 pg/g (range < 3.1-390 pg/g). Lipid adjustment of the data did not alter the distribution. Bivariate and multivariate analyses using selected demographic variables showed only marginal relationships between race/ethnicity and sex/fasting status with serum ME concentrations. Although no demographic variable was a good predictor of ME exposure or dose, our data indicate prevalent exposure of U.S. adults to ME. Detailed pharmacokinetic studies are required to determine the relationship between ME intake and human serum ME concentrations.

Seasonal dietary stress in a forest monkey (Cercopithecus mitis).

Blue monkeys (Cercopithecus mitis nyasae Schwarz) were studied for a period of 15 months on the Zomba Plateau in Malawi, which experiences pronounced seasonality of climate. 2) As might be expected, the monkey's diet contained most protein per item, and least potential digestion inhibitors, during the warm rainy season of the Malawian summer. 3) During the period, however, from October to November, which constitutes the hottest time of the year when the greatest number of trees are flowering and fruiting, protein intake was relatively lower than at other times of year and digestion-inhibitor intake tended to be relatively higher. 4) In the same period, the monkeys ranged more widely than during the winter months, when suitable food was available on the fewest number of tree species. 5) During the winter months, which occur in the first part of the dry season, the monkeys were able to obtain a reasonably nutritious diet from foliar material and some flowers, without recourse to any significant amount of fruit. 6) It is suggested that poor quality of diet during October and November is related to increased chemical defences in edible plant parts which may be partly the result of climatic pressures, and that the monkey's flexible response reflects a high degree of sensitivity to the chemical makeup of such plant parts.

Quantification of selected pesticide metabolites in human urine using isotope dilution high-performance liquid chromatography/tandem mass spectrometry.

The annual domestic use of pesticides is continually increasing, virtually ensuring that everyone is exposed to some level of pesticides on a regular basis through diet or environment. The potential developmental and physical adverse effects these chronic pesticide exposures have on children are of increasing concern. To adequately evaluate the potential adverse effects resulting from these exposures, accurate methods to measure the amount of the pesticide absorbed by the body must be developed. We have developed a sensitive method to measure the urinary metabolites of atrazine, diazinon, malathion, 2,4-dichlorophenoxyacetic acid (2,4-D), and certain synthetic pyrethroids in human urine. In our method, stable isotopically labeled analogues of the metabolites were spiked into the urine, which was subsequently extracted at both a neutral and acidic pH using organic solvents. The extracts were analyzed by high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) using atmospheric pressure chemical ionization. Our method has limits of detection ranging from 20 to 500 ng/l (parts per trillion) and relative standard deviations of less than 11%. This method has been used to measure the internal doses of these pesticides in both adults and children (n = 130) with no documented exposure to the pesticides. We detected atrazine and synthetic pyrethroid metabolites in less than 12% of the samples analyzed. The metabolites of 2,4-D, malathion, and diazinon were detected in 22%, 32%, and 57% of the samples, respectively.

Generalized resistance to thyroid hormone associated with possible selective cardiac nonresistance.

OBJECTIVE: To review the condition of generalized resistance to thyroid hormone and to report a case of generalized thyroid hormone resistance associated with atrial fibrillation. METHODS: A case report is presented of a 52-year-old man with atrial fibrillation who was referred by a cardiologist for thyroid ablation because of "hyperthyroidism," when his free thyroxine was found to be 4.35 ng/dL (normal, 0.55 to 2.46) and his free triiodothyronine was 6.5 pg/mL (normal, 1.4 to 4.4). RESULTS: This clinically euthyroid man with no signs or symptoms of hyperthyroidism except for the possibly related atrial fibrillation had a thyrotropin level of 3.45 mIU/L (normal, 0.46 to 4.7) in conjunction with the aforementioned increased levels of thyroid hormones. Further evaluation revealed normal 6-hour (11.7%) and 24-hour (27.6%) (123)I uptakes. Magnetic resonance imaging of the pituitary revealed a normal-sized gland with no masses. CONCLUSION: This is a rare case of generalized resistance to thyroid hormone in a patient with only atrial fibrillation. Whether the heart was selectively nonresistant to thyroid hormone as the cause of his atrial fibrillation or whether his atrial fibrillation was due to his mitral valve prolapse documented on echocardiography could not be determined with certainty. His ventricular rate of 83 per minute and laboratory evaluation suggest that thyroid hormone was not the cause of the atrial fibrillation.

The use of purified mucus glycoprotein gels in the assessment of mucolytic activity.

The effects of a wide range of mucolytic agents on the viscoelastic nature of a purified mucus glycoprotein gel have been investigated. The gel was produced by ultrafiltration of a solution containing high molecular weight glycoproteins obtained by gel chromatography in potassium thiocyanate. The fact that compounds as diverse as dithiothreitol and protease reduced the viscoelastic properties indicates that the model gel is appropriate for screening such compounds. Since it is homogenous and highly reproducible then it would appear to be ideal for such purposes. Also, it has been shown that mucus gels can be formed containing nothing but glycoproteins.

Splenic infarct presenting as acute abdominal pain in an older patient.

A 67-year-old female presented to the Emergency Department with a several hour history of severe pain in the left upper quadrant. A computed tomographic study (CT scan) of the abdomen demonstrated a splenic infarct. The patient was subsequently found to have a patent foramen ovale, with a small right-to-left shunt. This patient's splenic infarct is considered to be embolic in etiology, either from the patent foramen ovale or severe atherosclerotic disease. Patients with left upper quadrant pain who do not have the etiology differentiated by initial testing should be considered to have the potential for splenic infarction. This case illustrates the uncommon occurrence of splenic infarction, presenting as left upper quadrant pain.

Laboratory animal allergy: the measurement of airborne urinary allergens and the effects of different environmental conditions.

Casella Simquad air samplers, with 0.5 microM cut-off filters, were employed to sample the air in a laboratory animal house environment. The extracts obtained were assayed for laboratory animal urinary protein allergens using the inhibition radioallergosorbent test (RAST inhibition). The results showed that the collection and assay methods were of value and studies were extended to the influence of air change rates and humidity on airborne allergen levels. Reducing the air changes increased allergen levels, whilst increasing the humidity from 54% to 77% caused a significant reduction in allergen levels.

Genetic dissection of quantitative trait locus for ethanol sensitivity in long- and short-sleep mice.

Interval-specific congenic strains (ISCS) allow fine mapping of a quantitative trait locus (QTL), narrowing its confidence interval by an order of magnitude or more. In earlier work, we mapped four QTL specifying differential ethanol sensitivity, assessed by loss of righting reflex because of ethanol (LORE), in the inbred long-sleep (ILS) and inbred short-sleep (ISS) strains, accounting for approximately 50% of the genetic variance for this trait. Subsequently, we generated reciprocal congenic strains in which each full QTL interval from ILS was bred onto the ISS background and vice versa. An earlier paper reported construction and results of the ISCS on the ISS background; here, we describe this process and report results on the ILS background. We developed multiple ISCS for each Lore QTL in which the QTL interval was broken into a number of smaller intervals. For each of the four QTL regions (chromosomes 1, 2, 11 and 15), we were successful in reducing the intervals significantly. Multiple, positive strains were overlapped to generate a single, reduced interval. Subsequently, this reduced region was overlaid on previous reductions from the ISS background congenics, resulting in substantial reductions in all QTL regions by approximately 75% from the initial mapping study. Genes with sequence or expression polymorphisms in the reduced intervals are potential candidates; evidence for these is presented. Genetic background effects can be important in detection of single QTL; combining this information with the generation of congenics on both backgrounds, as described here, is a powerful approach for fine mapping QTL.

Complications of shoulder dislocation.

Dislocations of the shoulder are the most common joint dislocations seen in the emergency department, and complications of shoulder dislocations are more frequent than is generally believed. It is vital that emergency physicians have current knowledge of complications associated with shoulder dislocations because of their important role in recognition and prevention. Delayed recognition of complications can have an impact on the long-term outcome of patients. Prompt recognition and follow-up are essential. Most references address reduction methods rather than recognition of specific complications. Emergency physicians have few opportunities to update their knowledge of complications of shoulder dislocations. This article briefly reviews mechanisms of shoulder dislocation and discusses complications in light of the mechanisms of injury.

Emergency department recognition of acquired ventricular septal defect.

Acute myocardial infarction associated with ventricular septal defect (VSD) occurs infrequently. When a patient with an acquired VSD presents to the emergency department (ED), prompt recognition is required because definitive treatment can greatly decrease mortality. We present the case of a 75-year-old woman with an acute myocardial infarction and a new heart murmur. The diagnosis of acquired VSD was made by echocardiography in the ED, and emergency surgical correction was arranged.

Anesthesia for trauma during wartime.

Trauma during wartime has been the scourge of the ages. Conventional anesthesia with ether has been available since 1846 when it was demonstrated in Boston by a dentist named William Morton. Subsequently, ether was used during the Mexican-American War in 1847, and chloroform was used during the Crimean War from 1854 to 1856. Nurse anesthetists have made substantial contributions to care of the war-injured by initiating acute airway management and resuscitation efforts and by the administration of anesthesia care for critically injured war casualties undergoing surgical procedures. They have further contributed to goodwill in war-torn areas by providing anesthesia care to many civilian children and adults living in these areas of conflict. The evolution of nurse anesthesia contributions to the treatment of traumatized war casualties is the central focus of this article.