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Biomedical subjects

H Levine

Publications and source records attributed to H Levine.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effects of spaceflight conditions on fertilization and embryogenesis in the sea urchin Lytechinus pictus.

Calcium loss and muscle atrophy are two of the main metabolic changes experienced by astronauts and crew members during exposure to microgravity in space. Calcium and cytoskeletal events were investigated within sea urchin embryos which were cultured in space under both microgravity and 1 g conditions. Embryos were fixed at time-points ranging from 3 h to 8 days after fertilization. Investigative emphasis was placed upon: (1) sperm-induced calcium-dependent exocytosis and cortical granule secretion, (2) membrane fusion of cortical granule and plasma membranes; (3) microfilament polymerization and microvilli elongation; and (5) embryonic development into morula, blastula, gastrula, and pluteus stages. For embryos cultured under microgravity conditions, the processes of cortical granule discharge, fusion of cortical granule membranes with the plasma membrane, elongation of microvilli and elevation of the fertilization coat were reduced in comparison with embryos cultured at 1 g in space and under normal conditions on Earth. Also, 4% of all cells undergoing division in microgravity showed abnormalities in the centrosome-centriole complex. These abnormalities were not observed within the 1 g flight and ground control specimens, indicating that significant alterations in sea urchin development processes occur under microgravity conditions.

Animals↗
PubMed1999

A thermodynamic model for receptor clustering.

Intracellular signaling often arises from ligand-induced oligomerization of cell surface receptors. This oligomerization or clustering process is fundamentally a cooperative behavior between near-neighbor receptor molecules; the properties of this cooperative process clearly affect the signal transduction. Recent investigations have revealed the molecular basis of receptor-receptor interactions, but a simple theoretical framework for using these data to predict cluster formation has been lacking. Here, we propose a simple, coarse-grained, phenomenological model for ligand-modulated receptor interactions and discuss its equilibrium properties via mean-field theory. The existence of a first-order transition for this model has immediate implications for the robustness of the cellular signaling response.

Diffusion↗
PubMed1999

Safety and toxicity of nonoxynol-9 gel as a rectal microbicide.

BACKGROUND AND OBJECTIVES: Methods of HIV and STD prevention, which can be controlled by the receptive partner, are a high priority for research and development. Studies on the safety of Nonoxynol-9 (N-9) on the vaginal mucosa have yielded conflicting results. No Phase I study has evaluated the effect of N-9 on the rectal mucosa. GOALS: To assess the safety of 52.5 mg of N-9 in a 1.5-g gel when applied one to four applicators per day to the rectum and penis. STUDY DESIGN: The study included 25 HIV-negative and 10 HIV-positive, monogamous gay male couples in which each partner was exclusively insertive or receptive while using N-9 gel. Each participant served as his own control during placebo gel use compared to during N-9 gel use. Receptive partners underwent anoscopic examination after 1 week of placebo use and after 2, 5, and 6 weeks of N-9 gel use, with rectal biopsies obtained after 1 week of placebo use and after 5 and 6 weeks of N-9 gel use. Insertive partners had safety monitoring after 1 week of placebo use and after 2, 5, and 6 weeks of N-9. RESULTS: No rectal ulcers were detected; superficial rectal erosions were noted in two HIV-negative participants. Abnormal or slightly abnormal histologic abnormalities of rectal biopsies were detected in 31 (89%) receptive participants after N-9 gel use compared to 24 (69%) participants after 1 week of placebo gel use. Meatal ulceration, not caused by herpes simplex virus, was detected in one HIV-negative participant. CONCLUSION: Low-dose N-9 gel was not associated with macroscopic rectal and penile epithelial disruption or inflammation, but histologic abnormalities were commonly observed during N-9 gel as well as during placebo gel use.

Adult↗
PubMed1999

Steady-state cracks in viscoelastic lattice models.

We study the steady-state motion of mode III cracks propagating on a lattice exhibiting viscoelastic dynamics. The introduction of a Kelvin viscosity eta allows for a direct comparison between lattice results and continuum treatments. Utilizing both numerical and analytical (Wiener-Hopf) techniques, we explore this comparison as a function of the driving displacement Delta and the number of transverse rows N. At any N, the continuum theory misses the lattice-trapping phenomenon; this is well known, but the introduction of eta introduces some new twists. More importantly, for large N even at large Delta, the standard two-dimensional elastodynamics approach completely misses the eta-dependent velocity selection, as this selection disappears completely in the leading order naive continuum limit of the lattice problem.

Journal Article↗
PubMed1999

Arrested cracks in nonlinear lattice models of brittle fracture.

We generalize lattice models of brittle fracture to arbitrary nonlinear force laws and study the existence of arrested semi-infinite cracks. Unlike what is seen in the discontinuous case studied to date, the range in driving displacement for which these arrested cracks exist is very small. Also, our results indicate that small changes in the vicinity of the crack tip can have an extremely large effect on arrested cracks. Finally, we briefly discuss the possible relevance of our findings to recent experiments.

Journal Article↗
PubMed1999

Cell-sorting in aggregates of Dictyostelium discoideum.

When Dictyostelium cells are induced to develop between a coverslip and a layer of agarose, they aggregate normally into groups containing up to a thousand cells but are then constrained to form disks only a few cells thick that appear to be equivalent to the three-dimensional mounds formed on top of agarose. Such vertically restricted aggregates frequently develop into elongated motile structures, the flattened equivalent of three-dimensional slugs. The advantage of using this system is that the restricted z-dimension enables direct microscopic visualization of most of the cells in the developing structure. We have used time lapse digital fluorescence microscopy of Dictyostelium strains expressing green fluorescent protein (GFP) under the control of either prestalk or prespore specific promoters to follow cell sorting in these flattened mounds. We find that prestalk and prespore cells expressing GFP arise randomly in early aggregates and then rotate rapidly around the disk mixed with the other cell type. After a few hours, the cell types sort out by a process which involves striking changes in relative cell movement. Once sorted, the cell types move independently of each other showing very little heterotypic adhesion. When a group of prestalk cells reaches the edge of the disk, it moves out and is followed by the prespore cell mass. We suggest that sorting may result from cell type specific changes in adhesion and the consequent disruption of movement in the files of cells that are held together by end-to-end adhesion.

Animals↗
PubMed1998

Possible cooperation of differential adhesion and chemotaxis in mound formation of Dictyostelium.

In the mound stage of Dictyostelium discoideum, pre-stalk cells sort and form a tip at the apex. How this pattern forms is as yet unknown. A cellular level model allows us to simulate both differential cell adhesion and chemotaxis, to show that with differential adhesion only, pre-stalk cells move to the surface of the mound but form no tip. With chemotaxis driven by an outgoing circular wave only, a tip forms but contains both pre-stalk and pre-spore cells. Only for a narrow range of relative strengths between differential adhesion and chemotaxis can both mechanisms work in concert to form a tip containing only pre-stalk cells. The simulations provide a method to determine the processes necessary for patterning and suggest a series of further experiments.

Animals↗
PubMed1998

Malignancy-related hydrocephalus: clinical features and results of ventricular peritoneal shunt procedure in three patients.

Three patients with hydrocephalus secondary to central nervous system (CNS) metastases from lung or breast cancer are reviewed representing less than 5% of patients with CNS metastases seen at The Cancer Center of Boston over a 10-year period. The clinical picture is characterized by ataxia and mental confusion with dilated ventriculi on computed tomography (CT) scan of the brain. Computerized tomography of the brain and microscopic analysis of the cerebrospinal fluid are complementary in establishing the diagnosis of meningeal carcinomatosis. Surgical management by ventricular peritoneal shunt is an important component to multimodality therapy. The clinical course and extended survival in three patients provides a basis for recommending palliative surgical bypass as a therapeutic intervention with or without intrathecal chemotherapy, radiation, or both.

Aged↗
PubMed1997

Role of the CD40 and CD95 (APO-1/Fas) antigens in the apoptosis of human B-cell malignancies.

Ligation of CD40 inhibits apoptosis and stimulates proliferation of normal B cells, whereas ligation of CD95 (APO-1/Fas) induces apoptosis of activated lymphocytes. Aberrant signalling through the CD40 and CD95 antigens could thus participate in the pathogenesis of lymphoid malignancies. The expression and function of CD40 and CD95 on neoplastic B cells from patients with acute lymphoblastic leukaemia (ALL), chronic lymphocytic leukaemia (CLL) and non-Hodgkin's lymphoma (NHL) were examined. CD40 was expressed by all 30 B-cell tumours, whereas CD95 was detected on neoplastic B cells in only one of 10 cases of ALL, two of 10 cases of CLL, and three of 10 cases of NHL. Incubation with an agonistic CD95 monoclonal antibody (MoAb) did not augment apoptosis in any of the unstimulated B-cell neoplasms. CD40 triggering did not consistently inhibit spontaneous apoptosis, but ultimately stimulated the growth of neoplastic B cells in most cases. Furthermore, CD40 activation led to up-regulation of the CD95 antigen in all 30 B-cell neoplasms. Ligation of CD95 on CD40-activated tumour cells augmented apoptosis in five of 10 ALL, three of 10 CLL, and nine of 10 NHL cases. The degree of apoptosis induced by CD95 triggering was greater for NHL cells than for ALL cells or CLL cells. Bcl-2 expression by ALL and NHL cells was substantially decreased after in vitro culture, whereas Bcl-2 expression by CLL cells was not significantly changed. However, there was no correlation between the level of Bcl-2 expression and sensitivity to CD95-mediated apoptosis. Thus, factors other than levels of CD95 and Bcl-2 determine susceptibility of malignant B cells to apoptosis after CD95 triggering. CD40-activated lymphoma cells appear to be very sensitive to CD95-mediated apoptosis, suggesting potential strategies for treatment of NHL. Elucidation of the mechanisms underlying resistance of ALL and CLL cells to CD95 triggering may facilitate the development of novel therapeutic approaches to these diseases as well.

Apoptosis↗
PubMed1997

A further exploration of the lesbian identity development process and its measurement.

This study explored the fit of Cass's (1979) model of homosexual identity formation (HIF) and the utilization of the Self Identity Questionnaire (Brady, 1983) with a sample of lesbian women. Purposes of the study were to evaluate assignment of HIF stage based on two self-report measures, to measure the relationship between aspects of self-concept and lesbian identity development, and to clarify the sequencing of developmental tasks in lesbian identity formation. Participants were 118 women who self-identified as lesbian or as questioning their sexuality. Results of the study indicated that relationships exist between self-reported and assigned HIF stage, that HIF stage correlates with self-concept, and that participants moved through key developmental tasks in the order predicted by Cass's (1979) model. In addition, age was found to have a relationship with HIF stage. The study provides limited support for the utility of the HIF model and its measurement.

Adolescent↗
PubMed1997

Evaluation of a vaginal moisturizer in baboons with decreasing ovarian function.

Decrease of estrogen concentrations in postmenopausal women leads to many urogenital problems including vaginal dryness, atrophy, stenosis, itching, and irritation, along with sexual dysfunction. Systemic estrogen replacement is effective in many women but may not be effective in others because estrogen therapy may be contraindicated for medical reasons. The reproductive tract in nonhuman female primates has been used successfully as a model for a variety of research including, but not limited to, anatomy and physiology, reproduction, cancer, infectious disease, and menopause. The baboon is especially valuable because of the similarity of its menstrual cycle to women's, prior research with this animal, and its adaptability to captivity. A nonhormonal, nonsystemic, bio-adhesive vaginal moisturizer was evaluated in baboons as a possible alternative to hormonal therapy for vaginal symptoms due to a decrease in estrogen concentrations. Eight baboons with decreasing ovarian function were used in a two-part study to evaluate vaginal health with pliability, elasticity, mucosal secretion, pH, and histologic features as criteria. The first study involved a single intravaginally administered dose of test product, with evaluation at 20 min and 24 h later. The second study consisted of five doses given at 24-h intervals, with daily evaluations for 9 consecutive days. There was marked improvement in vaginal pliability, elasticity, and secretions, with decreased pH and thickness of the vaginal epithelium. These effects appeared 1 or 2 days after drug administration, reached the maximum on day 4, and mostly decreased by day 8. However, increased secretions, vaginal elasticity, and vacuolization of the epithelium in biopsy specimens persisted to the last day of observation. The study results indicate the efficacy of the test product and the value of the baboon as a model to study decreasing ovarian function and vaginal health.

Animals↗
PubMed1996

Positive genetic feedback governs cAMP spiral wave formation in Dictyostelium.

The aggregation stage of the life cycle of Dictyostelium discoideum is governed by the chemotactic response of individual amoebae to excitable waves of cAMP. We modeled this process through a recently introduced hybrid automata-continuum scheme and used computer simulation to unravel the role of specific components of this complex developmental process. Our results indicated an essential role for positive feedback between the cAMP signaling and the expression of the genes encoding the signal transduction and response machinery.

Animals↗
PubMed1996

Comparison of spermicides on vulvar, vaginal, and cervical mucosa.

The objective of this study was to compare the tolerability of Advantage 24 to two other spermicides containing non-oxynol-9 (N-9). These spermicides were Today Sponge (Sponge) and Conceptrol. In order to examine the incidence of complaints and the clinical observation of vaginal ulceration and irritation of the three spermicides, a randomized, open label, three period cross-over trial was conducted. Thirty-three women, ages 18-45, with a normal vaginal environment based on physical exam, Pap smear, vaginal wet prep, colposcopy, and serum N-9 were randomized into four treatment groups. Each treatment was for seven consecutive days with a 21-day washout. Data obtained were studied by one-way analysis of variance, chi-square, and Kruskal-Wallis test. No vulvar or vaginal abnormality was observed from either spermicide. Subjects had fewer and less severe cervical lesions by colposcopy during treatment with Advantage 24 than with Conceptrol or Sponge (p < 0.01). Comparison of the incidence of abnormal gynecological findings, serum N-9 levels, and the incidence of adverse events before and after treatment with the three study drugs indicate that most subjects had normal examinations pre- and post-treatment. Pap smear and colposcopy changes from normal to abnormal accounted for about 50% of all gynecological findings during the Conceptrol and Sponge treatments, but less than 20% during treatment with Advantage 24. All serum N-9 levels were below the level of detection (< 1.9 microgram/ml). Advantage 24 is better tolerated than Conceptrol or the Sponge. Furthermore, the cervical mucosa appears to be less resilient to spermicides than vulvo-vaginal mucosa.

Adolescent↗