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Biomedical subjects

E Cohen

Publications and source records attributed to E Cohen.

At least 127 records · Page 7Linked to original sources

Behavioral effects of interleukin-1 beta: modulation by gender, estrus cycle, and progesterone.

Endogenous release or exogenous administration of the cytokine Interleukin-1 (IL-1) produces several behavioral alterations, including suppression of locomotion and exploration. Because there are bidirectional interactions between IL-1 and the hypothalamic-pituitary-gonadal axis, we investigated possible differences between males and females in various phases of the estrus cycle in the behavioral effects of IL-1. In addition, we assessed the role of progesterone in mediating estrus cycle-dependent differences in these effects. Female rats in either the estrus or the non-estrus phase of their cycle and male rats were injected with either IL-1 beta (2 or 5 micrograms/kg) or saline. Activity in the open field test was measured 2 h later by counting the number of line crossings and rearings. In saline-injected rats, nonestrus females performed less line crossings than estrus females. IL-1 produced a significant dose-dependent reduction of line crossing in males and estrus females. In contrast, in nonestrus females the lower dose of IL-1 had no effect, and the effect of the higher dose was significantly smaller in nonestrus than in estrus females. The higher dose of IL-1 suppressed rearing in all three groups, but the effect of the lower dose on the number of rearings was significant only in estrus females. In a second experiment, ovariectomized females were injected with either progesterone (2 mg/rat) or oil, followed 2 h later by an injection of either IL-1 beta (2 micrograms/kg) or saline. Activity was measured continuously by a biotelemetric system. IL-1 reduced activity in progesterone-treated ovariectomized females but not in oil-injected controls. These findings suggest that changes in progesterone secretion along the estrus cycle modulate the behavioral responsiveness to IL-1 in female rats.

Animals↗

Antiviral properties of simple difunctionalized enols targeted to the HIV-1 protease.

The human immunodeficiency virus type 1 (HIV-1) protease catalyses the specific cleavage of the virion structural polyproteins p55gag and p160gag-pol and is, therefore, essential for viral maturation. We have previously reported a series of low molecular weight non-peptidic enol-based compounds that inhibit the HIV-1 protease activity in a competitive fashion (Vaillancourt et al., Bioorg. Med. Chem., 2 (1994) 343-355). Here we demonstrate that VS-215 and VS-261, two of these non-peptidic inhibitors, impair viral polyprotein maturation and exhibit antiviral activity in infected MT4 cells. The ID50 for these two compounds ranged between 24 and 50 microM whereas their TD50 ranged between 60 and 200 microM depending on the cell lines used. The calculated therapeutic index of these two inhibitors both had values of 2.5 even though they were shown to be non cytotoxic at their ID50. Their calculated permeability index ranged between 0.09 and 0.79 suggesting that these enol-based inhibitors efficiently reach the site of protease activity. These results provide new information on the therapeutic potential of this new class of protease inhibitors and emphasize the usefulness of enol chemistry in the development of anti-HIV-1 protease inhibitors.

Animals↗

Apical polarity in human colon carcinoma cell lines.

The non-polar human adenocarcinoma cells (HT29) when grown as monolayers or aggregates, have no tight junctions and no brush border. When these cells are treated with forskolin (15-100 microM) or cholera toxin (1 nM) intercellular lumina appear between the cells and about 30% of the cells facing the medium or the lumina are fully covered with a brush border. Aggregates embedded in collagen type I and treated with forskolin form a brush border only on cells facing the intercellular lumina. Monolayers of the polar human colon adenocarcinoma cell line Caco-2 express spontaneously tight junctions and a brush border in all the cells. When grown in aggregates the inner cells lose their polarity and only the cells facing the medium are polar. This polarity was not found when the aggregates were embedded in collagen gels. Aggregates embedded in collagen and treated with forskolin form bubble-like structures with a single layer of polar cells facing a central lumen. The data indicate that cell polarity is probably controlled by both internal factors such as cAMP and external factors such as cell-cell and cell-substratum molecules.

Cell Communication↗

Incidence of malposition of polyvinylchloride and red rubber left-sided double-lumen tubes and clinical sequelae.

Currently, fiberoptic bronchoscopy (FB) is recommended for correct positioning of double-lumen endobronchial tubes (DLTs) because of the high incidence of malpositions not appreciated by clinical signs. The aims of this study were to assess whether clinical signs allow accurate confirmation of adequate positioning with left red rubber (RR) or polyvinyl-chloride (PVC) double-lumen tubes and to compare the incidence of malpositions between the two tubes. Another goal was to assess whether these malpositions, not appreciated by clinical assessment, adversely affected outcome. Twenty-one adult patients scheduled for elective thoracic surgery were randomly assigned to the RR (11 patients) or PVC group (10 patients). After endobronchial intubation, the position of the tubes was adjusted until clinically satisfactory lung separation had been achieved. A single investigator performed all the FB assessments were performed in the supine (SUP) and lateral positions. The anesthesiologists responsible for the clinical evaluation were "blinded" to the bronchoscopic findings. While in the SUP position, the tube was "too deep" to permit visualization of the carina during tracheal bronchoscopy in 5 patients (2 RR, 3 PVC). In 17 of 21 (10 RR, 7 PVC), the bronchial cuff could not be visualized, although in 1 patient (RR group), the cuff was overinflated and bulged out to partially obstruct the right main bronchus orifice. Bronchial bronchoscopy showed 4 of 11 patients in the RR group in whom the left upper lobe orifice was occluded compared with 1 only in the PVC group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Towards a history of European physical sensibility: pain in the later Middle Ages.

The study of pain in a historical context requires a consideration of the cultural context in which pain is sensed and expressed. This paper examines attitudes toward physical pain in the later Middle Ages in Europe from several standpoints: theology, law, and medicine. During the later Middle Ages attitudes toward pain shifted from rejection and a demand for impassivity as a mark of status to a conscious attempt to sense, express, and inflict as much pain as possible. Pain became a positive force, a useful tool for reaching a variety of truths. While this attitude stemmed from the religious wish to identify with Christ's passion, it permeated and affected all spheres of cultural expression and investigation. Late medieval medicine accepted pain, trying to relieve it only when it became dangerous to the patient. Given the existence of analgesic medicines at the time, this attitude is comprehensible only within the cultural context of that period.

Europe↗

Is voluntary control of breathing impaired in patients with chronic obstructive pulmonary disease?

1. To assess whether voluntary control of breathing is impaired in patients with chronic obstructive pulmonary disease, a group of such patients performed a tracking task, requiring volitional control of respiratory muscles. 2. Eight patients (mean age 60 years; mean ratio of forced expiratory volume in 1 s to forced vital capacity = 31%) took part in the study. Five of the seven patients in whom blood gas measurements were made were mildly hypoxaemic (PaO2 = 53-71 mmHg), and one of these was hypercapnic (PaCO2 = 55 mmHg). Each subject performed a compensatory ventilatory tracking task using a tracking system which comprised a fixed target displayed on a monitor screen and a cursor moving in a line bisecting the target. The position of the cursor was perturbed by a forcing function and patients were required to keep the cursor on the target by breathing in and out of a spirometer. 3. To allow for any non-specific deficiency in motor control, patients performed a similar manual tracking task, using their dominant arm to move a joystick. As a control group, 11 healthy subjects (mean age 58 years; mean ratio of forced expiratory volume in 1 s to forced vital capacity = 77%) underwent an identical experimental protocol. 4. Motor control performances were measured in terms of the error between the target position and the subject's positioning of the cursor. Indices of performance were the root mean square of the error and the averages of the zero errors (i.e. end expiration/arm movement towards the trunk) and the peak errors (i.e. end inspiration/arm movement from the trunk).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Substance abuse and lifestyle among an urban schizophrenic population: some observations.

While substance-abusing, schizophrenic populations have been the focus of recent research inquiries (Cuffel et al. 1993; Dixon et al. 1990; Drake et al. 1989; Miller and Tannenbaum, 1989; Mueser et al. 1990), few researchers have attempted to address the prevalence of drug and alcohol abuse among an urban, poor, predominantly minority schizophrenic patient group (Drake et al. 1989). Furthermore, we know of no published account that attempts to document, using ethnographic data, the strategies these patients use to acquire drugs and/or alcohol, and the lifestyles associated with such substance use. The majority of the patients in our research are African-American (roughly 80%) and almost all are on medical assistance, pointing to an indigent population with few external resources and little expendable income.

Adult↗

Genetic variation for resistance to chlorpyrifos in Drosophila melanogaster (Diptera: Drosophilidae) infesting grapes in Israel.

Five species of drosophilid flies were observed breeding in grapes growing in Israel; of these, 2 species, Drosophila melanogaster (Meigen) and D. simulans Sturtevant, are major pests. Natural populations of both species were sampled and tested for resistance to chlorpyrifos; the 2 more intensively sampled populations were D. melanogaster in commercial vineyards. One vineyard had been treated repeatedly with chlorpyrifos to control this secondary pest species; the other had never been treated with an organophosphorus compound. The LC50 to chlorpyrifos of a genetically heterogeneous line of D. melanogaster from the exposed population (Be'er Tuvia) was 99 ng/cm2, and the LC50 of a corresponding line from the unexposed population (Sde Eliahu) was 52 ng/cm2; the wild-caught lines were much more resistant than a laboratory strain, Canton-S, whose LC50 was 0.25 ng/cm2. Genetic variance for resistance existed in both natural populations but realized heritability did not differ significantly between the populations. In crosses between a highly resistant strain and several sensitive laboratory strains of D. melanogaster, resistance was dominant. A resistance factor was mapped to a locus on chromosome 2 (approximately 2-72).

Animals↗

Early psychosocial risks for adolescent suicidal ideation and attempts.

OBJECTIVE: An ongoing, 14-year, longitudinal community study examined psychosocial risks for adolescent suicidal ideation and attempts, as well as the link between earlier suicidal behavior and later functioning. METHOD: Nearly 400 youths were followed between the ages of 5 and 18 years. Suicidal ideation was assessed at age 15 and lifetime suicide attempts were determined at age 18. Risk factors covered developmental periods from birth to age 15, and most were measured prospectively using multiple informants. Late-adolescent functioning (at age 18) was based on both self-reports and school records. RESULTS: For both genders, the early onset (by age 14) of psychiatric disorders significantly increased the risk for suicidal ideation at age 15 and suicide attempts by age 18. Early gender-specific risks for suicidal ideation included preschool behaviors that are counter to typical gender norms, such as aggressive behavior in females and dependence in males. Suicidal ideation at age 15 and suicide attempts were both associated with deficits in later adolescence (at age 18) in behavioral and social-emotional functioning. CONCLUSIONS: Suicidal ideation at age 15 was a marker of distress with long-term implications for later functioning. The early gender-specific risk factors for suicidal behavior identified in this study can aid in developing strategies for prevention and early intervention.

Adolescent↗

Traumas and posttraumatic stress disorder in a community population of older adolescents.

OBJECTIVE: The prevalence of DSM-III-R traumas and posttraumatic stress disorder (PTSD) and their impact on psychosocial functioning were examined in a community population of older adolescents. METHODS: Subjects were 384 adolescents participating in an ongoing longitudinal study. When subjects were aged 18 years, the NIMH Diagnostic Interview Schedule, Version IIIR, was used to identify lifetime traumatic events and diagnoses of PTSD, major depression, phobias, and substance dependence. Behavioral, emotional, and academic functioning in later adolescence was evaluated through self-report measures and school records. RESULTS: More than two fifths of adolescents experienced at least one DSM-III-R trauma by age 18 years; PTSD developed in 14.5% of these affected youths or 6.3% of the total sample. Youths with PTSD demonstrated widespread impairment at age 18, including more overall behavioral-emotional problems, interpersonal problems, academic failure, suicidal behavior, and health problems, as well as an increased risk for additional disorders. An equally striking finding was that youths who experienced traumas but did not develop PTSD also showed deficits in many of these areas when compared with their peers who had not experienced traumas. CONCLUSIONS: The substantial risk faced by youths in community settings for experiencing traumas and PTSD, along with associated impairments in later adolescence, underscores the need for programs of prompt intervention.

Achievement↗

Characterization of dynamic state inhibitors of HIV-1 protease.

The inhibitory behavior of simple N-protected amino acids containing a dysfunctional enol group was analyzed. Pseudo-Hill coefficients below 0.5 were obtained for the enol compounds. The active moiety of the enols described herein is involved in an equilibrium between keto and enol forms. The enol in its E form interacts strongly with the enzyme and we suggest that the Z form is expelled from the active site, as suggested by molecular modeling studies using the docking technique. Also, tetrahedral intermediate mimicry is achieved by the enol form, but not by the corresponding keto form. A pseudo-Hill coefficient of 0.25 has been determined for the Boc-phenylalanine enol, and by multiplying the concentration of inhibitor by its pseudo-Hill coefficient, a Ki of 0.82 microM has been determined for the inhibitory E-enol form. Boc-tyrosine enol generated a Ki of 0.39 microM. The requirements at the P1' position to achieve good inhibition are also described.

Amino Acid Sequence↗

Spindle cell lipomas. A report of two cases: one with multiple lesions.

BACKGROUND: Spindle cell lipoma is an unusual and histologically distinctive form of lipoma occurring primarily in older individuals. OBJECTIVE: The dermatologic surgeon and pathologist should be familiar with this variant of lipoma. METHODS: We are reporting two cases of spindle cell lipomas with the results of histologic examination with special stains and immunohistochemical studies. RESULTS: The neoplasms consisted of lobulated masses of mature adipose tissue with areas of spindle cell proliferation. There was strong positive staining with antibodies for vimentin within the areas of spindle cells proliferation. One of the cases is unusual in that multiple lesions are occurring in a young patient. CONCLUSION: Recognition of the histologic pattern is important in distinguishing the benign spindle cell lipoma from the malignant liposarcoma.

Adipose Tissue↗