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Biomedical subjects

S Levin

Publications and source records attributed to S Levin.

At least 37 records · Page 2Linked to original sources
PubMed1991

Fast cell membrane displacements in B lymphocytes. Modulation by dihydrocytochalasin B and colchicine.

A novel type of cell membrane movement was characterized in B lymphocytes. Local submicron cell membrane displacements, within the frequency range 0.3-15 Hz, were registered in a murine lymphoma B cell line by a novel optical method based on point dark field microscopy. The cell membrane displacements were measured by monitoring changes in light scattering from very small illuminated areas (0.25 microns2) at the edge of the cell surface. B lymphocytes manifest a relative change in light scattering of 7.7 +/- 1.3% (mean +/- SD) which corresponds to cell membrane transverse displacement of 131 +/- 22 nm. The confinement of cell membrane displacements to microdomains (less than or equal to 0.2 microns2) emerged from the observed dependence of the displacement amplitude on the area size from which it is monitored. Colchicine (1 microM) decreased membrane fluctuations down to a value of 88 +/- 14 nm, whereas dihydrocytochalasin B (2 microM) increased the amplitude of membrane displacements up to 184 +/- 31 nm. These findings demonstrate the existence of a dynamic mechanical interaction between the cytoskeleton and the cell membrane in the frequency range of 0.3-15 Hz. The modulation of these interactions by the disruption of microfilaments or or microtubules is explained in terms of the induced strain changes imposed on the cell membrane.

Animals↗
PubMed1991

Field flow fractionation in biomedical analysis.

Samples of biomedical interest which have been analysed by field-flow fractionation techniques are surveyed. The list begins with whole cells and microorganisms, going through viruses, nucleic acids, cell fragments and organelles, down to proteins and their aggregates. The principles of separation in the normal and steric mode of retention are illustrated, and instrumentation and techniques are described. The review concentrates mainly on the two systems of choice for biomedical applications: sedimentation and flow field-flow fractionation.

Cell Fractionation↗
PubMed1991

Continuous separation of particles from macromolecules in split-flow thin (SPLITT) cells.

A split-flow thin (SPLITT) cell with a perpendicular driving force of one gravity has been utilized for the rapid separation of micron-sized particles from macromolecules. The procedure involves the simultaneous use of two transport mechanisms and thus two operating modes: a sedimentation process controls the displacement of the particles across the thickness of the thin channel, while diffusion controls the displacement of macromolecules. The theoretical equations for these two operating modes are summarized and it is shown how the two modes can be combined to yield specified recovery factors. The theory was tested on a mixture of 10 microns polystyrene latex beads and three different proteins. The observed separation was in excellent agreement with theory. Attempts to fractionate red blood cells and plasma proteins from whole blood were only partially successful as a consequence of the weak sedimentation of red blood cells. Various remedies to this problem are suggested, the most promising of which is the use of a SPLITT cell subject to mild centrifugal forces.

Cell Fractionation↗
PubMed1991

6-trans-leukotriene B4 is a neutrophil chemotaxin in the guinea pig dermis.

The products of the 5- and 12-lipoxygenase (5-LO, 12-LO) pathways of arachidonic acid metabolism are implicated as proinflammatory mediators in a number of disease states. 12(R)-hydroxyeicosatetraenoic acid [12(R)-HETE] is present in large quantities in human psoriatic lesional skin and can be further metabolized by 5-LO to 5(S), 12(R)-dihydroxy-(6E,8Z,10E,14Z)-eicosatetraenoic acid (6-trans-LTB4). Furthermore, leukotriene B4 (LTB4) and the sulfidopeptide leukotrienes (LTC4, LTD4) can be transformed to 6-trans-LTB4. When injected into the guinea pig dermis, 6-trans-LTB4 (1.0, 10.0, 20.0 micrograms/intradermal site) caused a significant (P less than 0.02) infiltration of polymorphonuclear leukocytes (PMN) at 4 hr as assessed by histology and the levels of the PMN marker enzyme myeloperoxidase. 6-trans-LTB4 is a more potent PMN chemoattractant than 12(R)-HETE in the guinea pig dermis but is far less potent than LTB4. Pharmacological interdiction of leukotriene production or receptor binding should take into account the proinflammatory activity of 6-trans-LTB4.

Animals↗
PubMed1991

Modulation of the chemotactic properties of complement fragments C5a and C3 by the anti-inflammatory agent, SC-41930.

Cleavage of the fifth component of complement yields C5a, a potent neutrophil (PMN) and eosinophil chemoattractant, and modulator of microvascular permeability. Similarly, but to a lesser degree, C3 increases vascular permeability and histamine release. SC-41930 (7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)-propoxy]-3,4-dihydro-8- propyl- 2H-1-benzopyran-2-carboxylic acid), an orally-active antiinflammatory agent was tested in an in vivo model of dermal PMN chemotaxis induced by r-hu-C5a and hu-C3. Intradermal injection of C5a in the guinea pig resulted in a significant dose-dependent influx of PMNs at 4 hours as assessed by the dermal levels of myeloperoxidase (MPO). SC-41930 (20 mg/kg) given orally to guinea pigs with intradermal injections of 1 microgram C5a significantly (p less than 0.001) reduced dermal MPO content. SC-41930 was less potent against C3, requiring 40 mg/kg to significantly reduce dermal MPO levels. Agents such as SC-41930, which nullify complement's proinflammatory properties, may well have therapeutic potential.

Animals↗
PubMed1991

Effect of the leukotriene B4 receptor antagonist, SC-41930, on experimental allergic encephalomyelitis (EAE) in the guinea pig.

The accepted model for the human demyelinating disease, multiple sclerosis (MS), is experimental allergic encephalomyelitis (EAE). We assessed the ability of SC-41930(7-[3(4-acetyl-3-methoxy-2-propyl-phenoxy)-propoxy]- 3,4-dihydro-8-propyl-2H-1-benzopyran-2-carboxyl acid), to modulate the symptoms of acute EAE generated in guinea pigs. Animals were pretreated with SC-41930 (20 mg/kg, i.p.) for two days followed by thrice-weekly maintenance. At day 52, a significant number of the SC-41930-treated animals were alive as compared to EAE alone. Control animals had an increase in body weight while EAE animals lost over 20% (p less than 0.5) of their body weight by day 18. SC-41930-treatment significantly reduced, but did not completely inhibit the cachectic response. The results indirectly implicate LTB4 in the pathogenesis of EAE. Agents that modify this model be useful in the treatment of human MS.

Animals↗
PubMed1991

Membrane fluctuations in erythrocytes are linked to MgATP-dependent dynamic assembly of the membrane skeleton.

The observation of low-frequency fluctuations of the cell membrane in erythrocytes and in several nucleated cells suggests that this phenomenon may be a general property of the living cell. A study of these fluctuations in human erythrocytes and its ghosts has now been carried out using a novel optical method based on point dark field microscopy. We have demonstrated that the reestablishment of membrane fluctuations in erythrocyte ghosts is dependent on MgATP but does not necessarily require the restoration of the biconcave shape. The results imply that the dominant component of membrane fluctuations are metabolically dependent and suggest the existence of a dynamic mechano-chemical coupling within the membrane skeleton network induced by MgATP.

Adenosine Triphosphate↗
PubMed1991

The Pawtucket Heart Health Program. Influencing adolescent eating patterns.

The Pawtucket Heart Health Program, a research effort testing a process of community activation for cardiovascular risk factor behavior change, risk factor change, and coronary heart disease event rate change, utilizes risk factor behavior change programs for the entire population of a northeastern city. A diversity of nutrition programs designed to teach new skills and to alter the nutrition environment have been delivered. These include group programs, highlighting restaurant menus, labeling grocery shelf items, screening for blood cholesterol levels accompanied by nutritional counseling, and provision of programs in schools. In addition to standard curricula, the Heart Healthy Cook-Off for both junior high school and high school students has been developed. Students select recipes, make substitutions to lower fat, saturated fat, and cholesterol content, analyze original and substitution recipe nutrient content using a microcomputer and nutrient analysis software, and prepare the food. A panel of judges assesses presentation, taste, and health-promoting characteristics. In one junior high school class, cholesterol measure before and after the cook-off decreased by 10.7% among those with elevated cholesterol. The Heart Healthy Cook-Off is an education program that influences the culinary practices of children in an enjoyable, challenging format.

Adolescent↗
PubMed1991

Effects of the prostaglandin analogue misoprostol on cell proliferation in the canine small intestine.

While there are several reports of prostaglandins of the E series being associated with increased mucosal mass in the stomach, their effects on the small intestine are less well documented. A microdissection-based technique was used to measure proliferation and crypt size in the duodenum, jejunum and ileum of dogs given the prostaglandin analogue misoprostol. Six test and six control animals were given an oral dose of 300 micrograms kg-1 day-1 of misoprostol for 11 weeks, a dose-duration combination chosen to optimize the development of gastric hyperplasia. Misoprostol increased both the area of the crypts (P less than 0.001) and the number of mitoses per crypt (P = 0.002) throughout the small intestine. The technique also demonstrated a significant gradient in crypt size and in crypt area from the duodenum to the ileum. There was no statistical interaction between misoprostol and the site studied, suggesting that this trophic effect was systemic or systemically mediated.

Animals↗
PubMed1991

Quinidine-induced hepatotoxicity revisited.

Although quinidine has been widely used since the beginning of the century, quinidine-induced hepatotoxicity has been recently reported in the literature. We describe a reversible case of quinidine-induced hepatotoxicity. A 62-y-old male with a past medical history of atrial flutter and adult onset diabetes was admitted to the hospital with a 3-d history of diarrhea, nausea, fever, chills and palpitations. Past medications included 7.5 mg glyburide daily for 4 y, 0.25 mg digoxin daily for 3 w, 324 mg quinidine gluconate 3 times daily for 2 w, and 150 mg papaverine daily for 2 y. On admission, liver enzyme levels were elevated (SGOT 606, SGPT 1104). Quinidine was considered an etiologic agent and was discontinued after administration of 1 dose. The patient became afebrile within 48 h, liver enzyme levels gradually decreased, and the patient was discharged on day 6 of hospitalization. Repeat enzyme levels obtained 12 d after discharge were mostly within normal limits. The symptoms were atypical as described in the literature. We conclude that unexplained fever or elevated liver enzyme levels should alert the clinician to the possibility of quinidine-induced hepatotoxicity.

Chemical and Drug Induced Liver Injury↗
PubMed1991

A controlled comparison of involuntarily hospitalized medication refusers and acceptors.

Involuntarily hospitalized psychiatric patients consecutively admitted over a six-month period who successfully refused medication (n = 37) are compared with a randomly selected group of medication-accepting patients committed during the same time period (n = 37). The overall refusal rate was 15.6 percent during the study period. Acceptors and refusers did not differ on age, sex, diagnosis, ethnicity, marital status, or preadmission living status. Differences between the groups indicate that refusers are sicker and lower functioning, are more behaviorally acute on the ward, and stay in the hospital twice as long as acceptors. Refusers also have a significantly negative impact on the overall ward milieu. The impact of institutional factors on the rate and outcome from mediation refusal are discussed.

Adult↗
PubMed1991

Prostaglandins and the colonic epithelium. Effects of misoprostol on crypt size, cell production, and cell migration in the dog.

Colonic epithelial cell division, cell migration, and cell transit were investigated in dogs given 300 micrograms.kg-1.day-1 of the prostaglandin E1 analogue, misoprostol, for 11 weeks. The animals were then injected with [3H]thymidine and killed at timed intervals. The distribution of labeled and mitotic cells within the crypts was determined by scoring autoradiographs. There were no significant differences in mitotic index or labeling index between the two groups. The data were pooled and converted to give crypt cell production rates of 51.1 +/- 11.1 (control) and 58.24 +/- 8.6 cells per crypt per hour (test). However, the crypt length and cell population were slightly, but significantly, greater in the misoprostol-treated group (P less than 0.01). The movement of the wave of labeled cells with time after injection was used to calculate the median cell migration rates, which were 23.50 +/- 3.03 cell positions per day (control) and 18.30 +/- 2.56 (test). Thus, misoprostol had no significant effect on either the cell migration rate or the transit rates.

Animals↗
PubMed1990

Empiric antibiotic use--aztreonam as a model.

Empiric antibiotic therapy, which accounts for over 90 percent of in-hospital therapeutic antibiotic decisions, may be defined as tentative therapy designed to decrease morbidity and mortality associated with severe infection due to unidentified bacterial pathogens. In the 48- to 72-hour interim between presentation and the availability of reliable culture and sensitivity data that allow for definitive therapy, empiric therapy is extremely important. Aztreonam, the first member of the monobactam class of monocyclic beta-lactam antibiotics, is highly active against most gram-negative aerobic bacteria, including Pseudomonas aeruginosa. Its spectrum of activity is similar to that of the aminoglycosides but without the toxicity associated with those agents. For this reason, aztreonam may play an important role in empiric therapy. Currently, it can be recommended as single-agent empiric therapy only for severe urinary tract infections, but in combination with a variety of other agents, it has proved useful against a wide range of bacterial infections, and in certain subgroups, such as penicillin-allergic patients, it may represent the treatment of choice. It is not yet clear whether aztreonam is superior to other relatively nontoxic agents, such as the third-generation cephalosporins or carbapenems, but there is little doubt that this new agent is a generally safe and effective drug for the treatment of suspected gram-negative sepsis.

Aztreonam↗
PubMed1990

A multicentre trial of the aldose-reductase inhibitor, tolrestat, in patients with symptomatic diabetic neuropathy.

The effects of the aldose-reductase inhibitor, tolrestat, on chronic symptomatic diabetic sensorimotor neuropathy were studied during a placebo-controlled, randomised, 52-week multicentre trial. Of the four tolrestat doses investigated, only the highest dose group, 200 mg once daily, showed subjective and objective benefit over baseline and placebo, and further analyses are confined to this group (n = 112) and placebo (n = 107). Painful and paraesthetic symptoms were analysed separately: improvement in paraesthetic symptoms were seen at one year (p = 0.04), though painful symptoms improved on both placebo and active therapies. Significant improvement in both tibial and peroneal motor nerve conduction velocities were seen at 52 weeks. Tolrestat 200 mg once daily was significantly better than placebo in producing concordant improvements in both motor nerve conduction velocities and paraesthetic symptom scores at 24 weeks (p = 0.01), 42 weeks (p = 0.01) and 52 weeks (p = 0.02). Long-term benefit [concordant improvement at 24 weeks maintained until 52 weeks] was seen in 28% of treated patients compared to 5% on placebo (p = 0.001). It is concluded that some sustained improvement in symptomatic diabetic neuropathy may be obtained following aldose-reductase inhibition with tolrestat 200 mg once daily.

Aldehyde Reductase↗
PubMed1990

Inflammation of guinea pig dermis. Effects of leukotriene B4 receptor antagonist, SC-41930.

Neutrophil (PMNL) infiltration is a prominent feature of human psoriasis. Psoriatic skin lesions contain abnormally high amounts of leukotriene B4 (LTB4), itself a potent PMNL chemoattractant both in vivo and in vitro. SC-41930 (7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)-propoxy]-3,4-dihydro-8- propyl-2H-1-benzopyran-2-carboxylic acid), an orally active LTB4 receptor antagonist, was tested topically in models of skin inflammation induced by 200 nmol of the calcium ionophore A23187 or 200 micrograms phorbol-12-myristate-13-acetate (PMA) applied topically to the guinea pig ear as assessed by ear weight, levels of the PMNL marker enzyme myeloperoxidase (MPO), and histological examination (PMA model) at 4 and 18 h respectively. When coapplied topically with A23187 or PMA, SC-41930 significantly inhibited epidermal inflammation with ED50 values of 0.6 and 4 mg, respectively. SC-41930 treatment also was associated with lowered dermal LTB4 levels in both models. The PMA-induced skin inflammation model also was assessed histologically and revealed acanthosis, edema, PMNL infiltration, and rete ridge prominence as long as 96 h after a single application that was completely inhibited by SC-41930 topical coapplication. Furthermore, oral treatment (40 mg/kg) significantly reduced edema and inflammatory cell infiltration in both models. These models possess many of the characteristics of human psoriasis, and agents such as SC-41930 that demonstrate activity in these models may well have therapeutic utility in the treatment of human psoriasis.

Administration, Cutaneous↗
PubMed1990

Colonic inflammation in the rabbit induced by phorbol-12-myristate-13-acetate.

Neutrophil (PMNL) infiltration of inflamed colonic tissue is a prominent feature of human inflammatory bowel disease (IBD). Colitis was established in New Zealand white rabbits by the intrarectal instillation of 1.5 mg/kg (in 10 ml 20% ethanol) phorbol-12-myristate-13-acetate (PMA) and assessed by visual grading of colonic inflammation, levels of the neutrophil marker enzyme myeloperoxidase (MPO), and histological examination. After 24 h there was a significant (P less than 0.001) increase in MPO levels in the PMA-treated colons compared to ethanol control. There was also increased inflammation based on visual scoring. Histologically, PMA-treated colons were necrotic with focal ulceration, heavy PMNL infiltration and edema at 24 h; by 96 h colitis was sustained with mild edema, crypt abscesses, and a staining pattern suggesting altered mucus quality. These results suggest that PMA-induced colitis in rabbits may be a new model of IBD in which to evaluate drugs known to mitigate the inflammatory process.

Animals↗