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Biomedical subjects

H Moskowitz

Publications and source records attributed to H Moskowitz.

At least 19 recordsLinked to original sources

Effects of alcohol and other drugs on driver performance.

In the past century we have learned that driving performance is impaired by alcohol even in low dosage, and that many other drugs are also linked to impairment. This paper is a summary of some of the more relevant studies in the past fifty years--an overview of our knowledge and unanswered questions. There is no evidence of a threshold blood alcohol (BAC) below which impairment does not occur, and there is no defined category of drivers who will not be impaired by alcohol. Alcohol increases not only the probability of collision, but also the probability of poor clinical outcome for injuries sustained when impaired by alcohol. This review samples the results of the myriad studies that have been performed during the last half century as experiments have moved from examination of simple sensory, perceptual and motor behaviours to more complex measures of cognitive functioning such as divided attention and mental workload. These more sophisticated studies show that significant impairment occurs at very low BACs (< 0.02 gm/100 ml). However, much remains to be determined regarding the more emotional aspects of behaviour, such as judgment, aggression and risk taking. Considering that the majority of alcohol related accidents occur at night, there is a need for increased examination on the role of fatigue, circadian cycles and sleep loss. The study of the effects of drugs other than alcohol is more complex because of the number of substances of potential interest, the difficulties estimating drug levels and the complexity of the drug/subject interactions. The drugs of current concern are marijuana, the benzodiazepines, other psychoactive medications, the stimulants and the narcotics. No one test or group of tests currently meets the need for detecting and documenting impairment, either in the laboratory or at the roadside.

Aggression↗

Serious injuries and deaths of adolescent girls resulting from interpersonal violence: characteristics and trends from the United States, 1989-1998.

BACKGROUND: Little published data are available concerning the death and disability of adolescent girls resulting from interpersonal violence (adolescents are defined as those aged 12-18 years in this study). OBJECTIVES: To determine whether there were sex differences in (a) the characteristics of those who were injured or died, (b) injury severity and outcomes, and (c) injury mechanism; and to describe time trends in these differences. DESIGN: Analysis of data concerning serious injuries due to assaults, recorded in the National Pediatric Trauma Registry (from January 1, 1989, through December 31, 1998), and homicides, recorded in the Web-Based Injury Statistics and Query Reporting System database (from January 1, 1990, through December 31, 1997). SETTING: Patient data from participating pediatric trauma centers (National Pediatric Trauma Registry) in 45 states and national death certificate data (Web-Based Injury Statistics and Query Reporting System). PATIENTS: Six hundred twelve adolescent girls who were seriously injured because of an assault were compared with 2656 adolescent boys who were seriously injured because of an assault. Three thousand four hundred eighty-seven adolescent girls who died due to a homicide were compared with 17 292 adolescent boys who died due to a homicide. RESULTS: Assaulted adolescent girls were more likely to have preexisting cognitive or psychosocial impairments than were adolescent boys (odds ratio, 1.68; 95% confidence interval, 1.12-2.51). Adolescent girls trended toward more injury-related impairments at discharge from the hospital (odds ratio, 1.16; 95% confidence interval, 0.92-1.47). Adolescent girls were more likely to have been stabbed, and less likely to have been shot. Also, adolescent girls were more likely to have been injured at a home or a residence. Compared with all National Pediatric Trauma Registry admissions, assaults declined at the same rate for adolescent girls and boys. The proportion resulting from penetrating trauma declined more slowly for adolescent girls. CONCLUSIONS: Interpersonal violence causes considerable morbidity and mortality for young women. Research and interventions should be developed to respond to adolescent girls who experience interpersonal violence.

Adolescent↗

Isolation of juvenile hormone esterase and its partial cDNA clone from the beetle, Tenebrio molitor.

Juvenile hormone esterase (JHE) plays an essential role in insect development. It is partially responsible for the clearance of juvenile hormone (JH) which regulates various aspects of insect development and reproduction. Because of its role in regulating JH titer, this enzyme has been targeted for development of biologically-based insecticides. JHE was partially purified from the beetle, Tenebrio molitor, using a transition state analog as the affinity ligand. Two forms of JHE were characterized by activity analysis, isoelectric focusing, two-dimensional SDS-PAGE and N-terminal sequence analysis. The esterase is associated with two proteins of sizes 71 and 150 kDa, both of which are active on JH III. A partial cDNA clone for the enzyme was isolated based on the sequence of N-terminal and internal peptides. Its sequence indicates that JHE from T. molitor and Heliothis virescens may have a common origin.

Animals↗

The effect of imaging guidelines on the number and quality of outpatient radiographic examinations.

OBJECTIVE: A significant percentage of outpatient diagnostic radiology is performed by nonradiologists. Studies have shown nonradiologists have higher utilization and cost, as well as quality problems. We sought to determine if, in a managed care environment, a set of guidelines limiting imaging privileges of nonradiologist physicians could decrease imaging costs while ensuring that equipment and personnel providing imaging were of the highest quality. MATERIALS AND METHODS: We determined the number and type of radiographic imaging studies performed the year after these guidelines were set in place (1997) and compared these findings with those of the year before the guidelines were established (1995) and with preguideline trends. We established quality criteria and, based thereon, inspected imaging offices. RESULTS: The number of radiographic examinations per 1000 enrollees decreased 20-25% from the previous trend. Nonradiologists' share of the total fell from 39% to 15%. No deficiencies were found in the inspection of five radiologists' offices, whereas significant deficiencies of equipment, equipment maintenance, or documentation of the examinations performed were found in 78% of nonradiologists' offices. None of the quality indicators monitored by the health plan showed significant change. CONCLUSION: Specific guidelines can effect change in the location and number of radiologic examinations performed, with an improvement in the quality of the studies and a decrease in radiation dose and cost. No decline in quality of care appears to result, despite claims by opponents to such changes that widespread serious quality impairment would occur.

Ambulatory Care↗

Police officers' detection of breath odors from alcohol ingestion.

Police officers frequently use the presence or absence of an alcohol breath odor for decisions on proceeding further into sobriety testing. Epidemiological studies report many false negative errors. The current study employed 20 experienced officers as observers to detect an alcohol odor from 14 subjects who were at blood alcohol concentrations (BACs) ranging from zero to 0.130 g/dl. Over a 4 h period, each officer had 24 opportunities to place his nose at the terminal end of a 6 in. tube through which subjects blew. Subjects were hidden behind screens with a slit for the tube to prevent any but odor cues. Under these optimum conditions, odor was detected only two-thirds of the time for BACs below 0.08 and 85% of the time for BACs at or above 0.08%. After food consumption, correct detections declined further. Officers were unable to recognize whether the alcohol beverage was beer, wine, bourbon or vodka. Odor strength estimates were unrelated to BAC levels. Estimates of BAC level failed to rise above random guesses. These results demonstrate that even under optimum laboratory conditions, breath odor detection is unreliable, which may account for the low detection rate found in roadside realistic conditions.

Adult↗

A depressant insect-selective toxin analog from the venom of the scorpion Leiurus quinquestriatus hebraeus--purification and structure/function characterization.

The scorpion venom-derived excitatory and depressant insect-selective polypeptide neurotoxins modify sodium conductance in insect neuronal membranes and differ greatly in their primary structures and symptoms induced in blow fly larvae. We report here the purification and characterization of a new insect selective toxin, LqhIT5. LqhIT5 is more similar to the excitatory toxins in its mode of action and the depressant toxins in its primary structure. This toxin is a single polypeptide composed of 61 amino acids that are cross linked by four disulfide bonds. When LqhIT5 is injected into blow fly larvae, a fast contraction paralysis occurs without depressant activity. No mammalian toxicity was detected by subcutaneous or intracranial injections of this toxin into mice. Sequence comparison of LqhIT5 and known depressant toxins shows a high degree of similarity among the amino acids located on the C-terminus of the toxins. However, there are some clear differences in the amino acids located close to the N-terminus of the toxins. By the aid of homology modeling, we demonstrated that these amino acids have the same orientation in the tertiary structure of the molecule and are exposed to the environment. The change in the mode of action of LqhIT5 (no depressant activity) by substitutions of a few amino acids located on a specific exposed area of the toxin shed a new light on the structure/function relationship of scorpion toxins. These results caution that similarity in the mechanism of action of scorpion toxins does not always follow from an overall similarity in sequence.

Amino Acid Sequence↗

Rapid purification and molecular modeling of AaIT peptides from venom of Androctonus australis.

As recombinant viruses expressing scorpion toxins are moving closer toward the market, it is important to obtain large amounts of pure toxin for biochemical characterization and the evaluation of biological activity in nontarget organisms. In the past, we purified a large amount of Androctonus australis anti-insect toxin (AaIT) present in the venom of A. australis with an analytical reversed-phase column by repeated runs of crude sample. We now report 20 times improved efficiency and speed of the purification by employing a preparative reversed-phase column. In just two consecutive HPLC steps, almost 1 mg of AaIT was obtained from 70 mg crude venom. Furthermore, additional AaIT was obtained from side fractions in a second HPLC run. Recently discovered insect selective toxin, AaIT5, was isolated simultaneously from the same venom batch. It shows different biological toxicity symptoms than the known excitatory and depressant insect toxins. AaIT5 gave 100% mortality with a dose of less than 1.3 micrograms against fourth-instar tobacco budworms Heliothis virescens 24 h after injection. During the purification process, we implemented mass spectrometry in addition to bioassays to monitor the presence of AaIT and AaIT5 in the HPLC fractions. Mass spectrometric screening can unambiguously follow the purification process and can greatly facilitate and expedite the downstream purification of AaIT and AaIT5 eliminating the number of bioassays required. Further, electrospray ionization was compared with matrix-assisted desorption/ionization and evaluated as a method of choice for mass spectrometric characterization of fractions from the venom purification for it provided higher mass accuracy and relative quantitation capability. Molecular models were built for AaIT5, excitatory toxin AaIT4, and depressant toxin LqhIT2. Three-dimensional structure of AaIT5 was compared with structures of the other two toxins, suggesting that AaIT5 is similar to depressant toxins.

Amino Acid Sequence↗

Anti-insect toxin 5 (AaIT5) from Androctonus australis.

An insect-selective scorpion toxin (AaIT5) was purified from the venom of the North African scorpion Androctonus australis, and its amino acid sequence was determined by a combination of automated Edman degradation, electrospray-ionization mass spectrometry, and sequence alignment. This insect toxin is very potent against the tobacco budworm, Heliothis virescens (100% lethal dose < 1.8 microg/100 mg body mass) and shows a distinct insect specificity and various symptoms. It is not toxic to mice after subcutaneous injection. The molecular mass of this toxin is 6882 Da and the amino acid sequence is similar to those of Androctonus australis anti-insect toxin 4 (AaIT4), Leiurus quinquestriatus depressant anti-insect toxins (LqhIT2, LqqIT2), and Buthotus judaicus depressant anti-insect toxin (BjIT2).

Amino Acid Sequence↗

Positive cooperativity among insecticidal scorpion neurotoxins.

The insecticidal activity of scorpion neurotoxic polypeptides increased 5-10-fold with no apparent increase in mammalian toxicity when a combination of two toxins was injected. Synergistic combinations could be predicted from binding studies and competitive displacement assays. Our results indicate that simultaneous expression in baculovirus or other transgenic organisms of the synergistic combinations of insecticidal toxins may result in more potent insect-selective biopesticides.

Animals↗

Recurrent mediastinal bronchogenic cyst.

A patient with a new mediastinal mass 25 years after resection of a mediastinal bronchogenic cyst is presented. Computed tomography and subsequent thoracotomy revealed a recurrent bronchogenic cyst. This case illustrates that incompletely resected mediastinal bronchogenic cysts may recur many years later.

Bronchogenic Cyst↗

The activity of 2-substituted quinoline alkaloids in BALB/c mice infected with Leishmania donovani.

Potent antileishmanial activity has recently been described in vivo when certain 2-substituted quinoline alkaloids are administered to mice with cutaneous leishmaniasis. We now report the antileishmanial activity of four 2-substituted quinoline alkaloids, namely chimanine D or 2-(1',2'-trans-epoxypropyl) quinoline (I), 2-n-propylquinoline (II), 2-styrylquinoline (III) and 2-(2'-hydroxypropyl) quinoline (IV), for experimental treatment of visceral leishmaniasis in infected BALB/c mice. Subcutaneous treatment with chimanine D for 10 days at 0.54 mmol/kg per day resulted in 86.6% parasite suppression in the liver. Oral administration of 0.54 mmol/kg of 2-n-propylquinoline once daily for 5 or 10 days to L. donovani-infected mice suppressed parasite burdens in liver by 87.8 and 99.9%, respectively. Cutaneous administration of meglumine antimonate for 10 days resulted in 97.4% parasite suppression in the liver. This study is, to our knowledge, the first to demonstrate the activity of 2-substituted quinoline alkaloids in experimental treatment of visceral leishmaniasis. Further biological and chemical studies of these products might yet prove helpful for the development of new antileishmanial drugs.

Alkaloids↗

Hepatobiliary study. Left hepatic lobe herniation into the thorax.

After a motor vehicle accident, an 18-year-old woman reported cough and dyspnea. A chest radiograph revealed an intrathoracic mass blending with the cardiac shadow. Hepatobiliary imaging showed that this was due to herniation of the left hepatic lobe and a portion of the right lobe and gallbladder into the right hemithorax.

Adolescent↗

Screening mammography: the Mount Sinai BreastCheck experience.

Early detection can result in a decrease in the death rate from breast cancer. Screening mammography is the most important modality available to discover early so-called "minimal" cancer. In an effort to make screening mammography more available to the women of north central Connecticut, Mount Sinai Hospital, a community based, university-affiliated hospital initiated a screening program five years ago. During the four-year interval on which we are reporting, we have screened almost 15,000 women using a mobile van. Seventy-seven cancers were discovered in this screened population, with a detection rate of five cancers per 1,000. Our biopsy rate was 1.5% with a positive predictive value of 34%. Sixty-one percent of the tumors discovered were so-called "minimal" cancers and only 12 of the 77 patients had positive lymph nodes.

Adult↗

Localization of receptor sites for insect-selective toxins on sodium channels by site-directed antibodies.

Site-directed antibodies corresponding to conserved putative extracellular segments of sodium channels, coupled with binding studies of radiolabeled insect-selective scorpion neurotoxins, were employed to clarify the relationship between the toxins' receptor sites and the insect sodium channel. (1) The depressant insect toxin LqhIT2 was shown to possess two noninteracting binding sites in locust neuronal membranes: a high-affinity (KD1 = 0.9 +/- 0.6 nM) and low-capacity (Bmax1 = 0.1 +/- 0.07 pmol/mg) binding site as well as a low-affinity (KD2 = 185 +/- 13 nM) and high-capacity (Bmax2 = 10.0 +/- 0.6 pmol/mg) binding site. (2) The high-affinity site serves as a target for binding competition by the excitatory insect toxin AaIT. (3) The binding of LqhIT2 was significantly inhibited in a dose-dependent manner by each of four site-directed antibodies. The binding inhibition resulted from reduction in the number of binding sites. (4) The antibody-mediated inhibition of [125I]AaIT binding differs from that of LqhIT2: three out of the four antibodies which inhibited LqhIT2 binding only partially affected AaIT binding. Two antibodies, one corresponding to extracellular and one to intracellular segments of the channel, did not affect the binding of either toxin. These data suggest that the receptors to the depressant and excitatory insect toxins (a) comprise an integral part of the insect sodium channel, (b) are formed by segments of external loops in domains I, III, and IV of the sodium channel, and (c) are localized in close proximity but are not identical in spite of the competitive interaction between these toxins.

Animals↗

Sedating effects of ethanol and time of drinking.

Ethanol (0.5 g/kg) was administered to 12 healthy, normal-sleeping men, aged 21 to 45, at two different times of the day (0900 and 1700 hr). The Multiple Sleep Latency Test (MSLT) was conducted at 1000, 1200, 1400, and 1600 hr in the day drinking condition and at 1800, 2000, 2200, and 2400 hr in the evening drinking condition. On placebo, sleepiness was greater in the daytime testing hours than in the evening, replicating findings on the circadian rhythm of sleepiness/alertness. There was a time of drinking (day versus evening) by ethanol interaction. An ethanol effect on sleep latency was found in the daytime hours, when alertness was relatively low. Ethanol failed to have a significant effect on sleep latency during the evening hours when alertness levels were increasing. Performance on a divided attention task, administered 1 hr postconsumption, was impaired by ethanol consumption, but did not vary as a function of time of drinking (day versus evening). However, at 5 hr postconsumption, mean reaction time on the first 20 min of a 40-min auditory vigilance task was slowed by ethanol to a greater extent after day drinking then after evening drinking.

Adult↗