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Biomedical subjects

H Moskowitz

Publications and source records attributed to H Moskowitz.

At least 19 recordsLinked to original sources

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

Solubilization and characterization of the insect neuronal sodium channel.

Locust neuronal sodium channels were solubilized by 1% cholate and 0.2% Triton X-100, and their functionality was monitored by [3H]saxitoxin (STX) binding assays. About 40% of STX binding activity was recovered in the solubilized fraction without affecting affinity (Kd = 0.5 nM) and the time and temperature dependent STX binding activity was significantly stabilized in the presence of 20 nM STX. Partial purification by an anion exchange resin yielded a 20% recovery and a 3.5 times increase in the specific STX binding activity. Identification of the locust solubilized sodium channels by immunoprecipitation and radiophosphorylation revealed a Mr of 245,000 on SDS-PAGE. The present solubilized preparation will enable the study of the unique pharmacology of insect sodium channels.

Animals

Sodium channel polypeptides in central nervous systems of various insects identified with site directed antibodies.

Immunoprecipitation, radiophosphorylation and SDS-PAGE autoradiography enable the characterization of sodium channel polypeptides in the central nervous system of insects belonging to four phylogenetically distinct orders: grasshoppers, cockroaches, flies and moth larvae. It has been shown that the insect sodium channels: (1) Are recognized by the previously described (Gordon et al. (1988) Biochemistry 27, 7032-7038) site directed antibodies corresponding to a highly conserved segment linking the homologous domains III and IV in the vertebrate sodium channel alpha subunits. (2) Serve as substrates for phosphorylation by cAMP-dependent protein kinase. (3) Are devoid of disulfide linkage to smaller subunits unlike sodium channels in vertebrate brain. (4) Are glycoproteins as shown in the grasshopper by the decrease of apparent molecular weight following endoglycosidase F treatment and specific binding to the lectins concanavalin A and wheat germ agglutinin. (5) Reveal a diversity with regard to their (a) apparent molecular masses which range from 240 to 280 kDa and (b) V8 proteinase digestion phosphopeptides indicating either differences in the positioning of the enzymatic cleavage and/or phosphorylation sites. These results provide the first evidence for structural diversity of sodium channel subtypes among various insect orders and are compared to their mammalian counterparts.

Amino Acid Sequence

Drug performance sensitivity: a pilot study.

Thirty noninsomniac healthy adult men were enrolled in a multicenter pilot study to evaluate the sensitivity of psychomotor and cognitive tasks and subjective evaluation of performance and mood after treatment with flurazepam (Dalmane) 45 mg (larger than the recommended prescribing dose of 15-30 mg). This pilot study was also used to standardize testing procedures. The subjects were given either flurazepam or placebo at 72-hour intervals in a double-blind Latin square crossover design. Choice reaction time, but not simple reaction time, was drug sensitive. Divided attention and vigilance tasks were also sensitive to drug effects. Of the two cognitive tasks tested, addition was impaired by drug, but reading comprehension was not. Subjective evaluations of performance and mood states indicate that these are useful measures, but responses on the Hopkins Symptom Checklist were not influenced.

Adult

Psychomotor performance in chronic insomniacs during 14-day use of flurazepam and midazolam.

Four skills performance (psychomotor) tasks, including simple and choice reaction time, divided attention, and vigilance, were given to 99 chronic insomniacs to determine whether the use of midazolam 15 mg, or of flurazepam 15 or 30 mg, compared with placebo would produce next-day impairment throughout a 14-day treatment period. Tests were administered during 2 baseline days and on treatment days 1 and 2 (early interval), 7 (middle interval) and 13 and 14 (late interval). Compared with placebo, performance on all four tasks was impaired by flurazepam 30 mg. The deficits associated with flurazepam 15 mg were roughly half the magnitude of those produced by flurazepam 30 mg, but these changes did not reach statistical significance for single response measures at single time intervals. Midazolam showed no consistent pattern of performance effects; however, for divided attention tracking error, there was a significant decrement. The placebo group showed flat performance curves or improved performance as a result of learning (practice effect).

Adult

Mobile mammography: the first six-months experience at Mount Sinai Hospital.

Mount Sinai Hospital's Mobile Mammography Program, BreastCheck, is designed to screen large numbers of women for breast cancer in the greater Hartford area. Despite the American Cancer Society recommendations for screening mammography, many physicians still are not complying with these guidelines. This report details our first six-months experience. Two thousand two hundred thirty women were screened, 38 women had biopsies, and 14 cancers were detected. The overall rate of breast cancer detection is 6.3/1,000 which compares favorably with the rates from the National Breast Cancer Demonstration Detection Project (BCDDP) of 4.6/1,000.

Adult

Effects of terfenadine, diphenhydramine, and placebo on skills performance.

The behavioral effects of the antihistamines terfenadine and diphenhydramine were compared in a placebo-controlled, double-blind crossover study. Performance of skills deemed important in safe man-machine interactions was objectively assessed one, three, and five hours after administration of test substances. The results indicate that diphenhydramine use resulted in various degrees of impairment of the ability to perform a visual-search task, a tracking task, a divided-attention task, and a vigilance task. Terfenadine users performed as well as or better than placebo-treated subjects. No differences between terfenadine and placebo were found on a subjective evaluation scale. Diphenhydramine users consistently reported feelings of impairment.

Adult

The effects on performance of two antidepressants, alone and in combination with diazepam.

1. Ninety healthy adult men participated in a study of the effects on performance of 60 mg fluoxetine, 50 mg amitriptyline or placebo, alone and in combination with 5 mg diazepam or placebo. 2. In a 2X3 factorial design study, groups of 15 Ss received one of six possible treatment combinations. 3. Ss were tested with a battery of laboratory tests at two post-dosing times. 4. Amitriptyline impaired the performance of all tasks. When diazepam was added to the amitriptyline treatment, the impairment of three tasks increased. Diazepam alone produced impairment on two measures. 5. Fluoxetine alone impaired no task; some impairment occurred with the fluoxetine-diazepam combination.

Adult

The methylation state of the proviruses in avian sarcoma virus transformed chick and rat cells.

The endogenous viruses in the avian cells are not completely methylated, nor are the Schmidt-Ruppin RSV-D (SRD) proviruses in the infected cells completely unmethylated. Avian sarcoma proviruses integrated in rat transformed cloned cells are heavily methylated. In these cells, a region in the 3' end of the env gene is unmethylated in all the src-containing proviruses but not in the transformed defective (td) proviruses. A possible role for the hypomethylation of the 3' end of the env region is proposed.

Animals