On the structure and dynamics of water associated with single-supported zwitterionic and anionic membranes.

We have used high-resolution quasielastic neutron scattering (QENS) to investigate the dynamics of water molecules (time scale of motion ∼10-11-10-9 s) in proximity to single-supported bilayers of the zwitterioniclipid DMPC (1,2-dimyristoyl-sn-glycero-3-phosphorylcholine) and the anionic lipid DMPG (1,2-dimyristoyl-sn-glycero-3-phosphoglycerol) in the temperature range 160-295 K. For both membranes, the temperature dependence of the intensity of neutronsscattered elastically and incoherently from these samples indicates a series of freezing/melting transitions of the membrane-associated water, which have not been observed in previous studies of multilayer membranes. We interpret these successive phase transitions as evidence of different types of water that are common to the two membranes and which are defined by their local environment: bulk-like water located furthest from the membrane and two types of confined water in closer proximity to the lipids. Specifically, we propose a water type termed "confined 2" located within and just above the lipid head groups of the membrane and confined 1 water that lies between the bulk-like and confined 2 water. Confined 1 water is only present at temperatures below the freezing point of bulk-like water. We then go on to determine the temperature dependence of the translational diffusion coefficient of the water associated with single-supported DMPG membranes containing two different amounts of water as we have previously done for DMPC. To our knowledge, there have been no previous studies comparing the dynamics of water in proximity to zwitterionic and anionic membranes. Our analysis of the water dynamics of the DMPG and DMPC membranes supports the classification of water types that we have inferred from their freezing/melting behavior. However, just as we observe large differences in the freezing/melting behavior between these model membranes for the same water type, our measurements demonstrate variation between these membranes in the dynamics of their associated water over a wide temperature range. In particular, there are differences in the diffusive motion of water closest to the lipid head groups. Previously, QENS spectra of the DMPC membranes have revealed the motion of water bound to the lipid head groups. For the DMPG membrane, we have found some evidence of such bound water molecules; but the signal is too weak for a quantitative analysis. However, we observe confined 2 water in the DMPG membrane to undergo slow translational diffusion in the head group region, which was unobserved for DMPC. The weak temperature dependence of its translational diffusion coefficient allows extrapolation to physiological temperatures for comparison with molecular dynamics simulations.

Evaluating the solid electrolyte interphase formed on silicon electrodes: a comparison of ex situ X-ray photoelectron spectroscopy and in situ neutron reflectometry.

This work details the in situ characterization of the interface between a silicon electrode and an electrolyte using a linear fluorinated solvent molecule, 0.1 M lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) in deuterated dimethyl perfluoroglutarate (d6-PF5M2) (1.87 × 10(-2) mS cm(-1)). The solid electrolyte interphase (SEI) composition and thickness determined via in situ neutron reflectometry (NR) and ex situ X-ray photoelectron spectroscopy (XPS) were compared. The data show that SEI expansion and contraction (breathing) during electrochemical cycling were observed via both techniques; however, ex situ XPS suggests that the SEI thickness increases during Si lithiation and decreases during delithiation, while in situ NR suggests the opposite. The most likely cause of this discrepancy is the selective removal of SEI components (top 20 nm of the SEI) during the electrode rinse process, which is required to remove the electrolyte residue prior to ex situ analysis, demonstrating the necessity of performing SEI characterization in situ.

Structure and dynamics of water and lipid molecules in charged anionic DMPG lipid bilayer membranes.

Molecular dynamics simulations have been used to investigate the influence of the valency of counter-ions on the structure of freestanding bilayer membranes of the anionic 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) lipid at 310 K and 1 atm. At this temperature, the membrane is in the fluid phase with a monovalent counter-ion and in the gel phase with a divalent counter-ion. The diffusion constant of water as a function of its depth in the membrane has been determined from mean-square-displacement calculations. Also, calculated incoherent quasielastic neutron scattering functions have been compared to experimental results and used to determine an average diffusion constant for all water molecules in the system. On extrapolating the diffusion constants inferred experimentally to a temperature of 310 K, reasonable agreement with the simulations is obtained. However, the experiments do not have the sensitivity to confirm the diffusion of a small component of water bound to the lipids as found in the simulations. In addition, the orientation of the dipole moment of the water molecules has been determined as a function of their depth in the membrane. Previous indirect estimates of the electrostatic potential within phospholipid membranes imply an enormous electric field of 10(8)-10(9) V m(-1), which is likely to have great significance in controlling the conformation of translocating membrane proteins and in the transfer of ions and molecules across the membrane. We have calculated the membrane potential for DMPG bilayers and found ∼1 V (∼2 ⋅ 10(8) V m(-1)) when in the fluid phase with a monovalent counter-ion and ∼1.4 V (∼2.8 ⋅ 10(8) V m(-1)) when in the gel phase with a divalent counter-ion. The number of water molecules for a fully hydrated DMPG membrane has been estimated to be 9.7 molecules per lipid in the gel phase and 17.5 molecules in the fluid phase, considerably smaller than inferred experimentally for 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC) membranes but comparable to the number inferred for 1,2-dilauroyl-sn-glycero-3-phosphoethanolamine (DLPE) membranes. Some of the properties of the DMPG membrane are compared with those of the neutral zwitterionic DMPC bilayer membrane at 303 K and 1 atm, which is the same reduced temperature with respect to the gel-to-fluid transition temperature as 310 K is for the DMPG bilayer membrane.

Diffusion of water and selected atoms in DMPC lipid bilayer membranes.

Molecular dynamics simulations have been used to determine the diffusion of water molecules as a function of their position in a fully hydrated freestanding 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC) bilayer membrane at 303 K and 1 atm. The diffusion rate of water in a ∼10 Šthick layer just outside the membrane surface is reduced on average by a factor of ∼2 relative to bulk. For water molecules penetrating deeper into the membrane, there is an increasing reduction in the average diffusion rate with up to one order of magnitude decrease for those deepest in the membrane. A comparison with the diffusion rate of selected atoms in the lipid molecules shows that ∼6 water molecules per lipid molecule move on the same time scale as the lipids and may therefore be considered to be tightly bound to them. The quasielastic neutron scattering functions for water and selected atoms in the lipid molecule have been simulated and compared to observed quasielastic neutron scattering spectra from single-supported bilayer DMPC membranes.

Large-scale sprouting of cortical connections after peripheral injury in adult macaque monkeys.

Distributions of thalamic and cortical connections were investigated in four macaque monkeys with long-standing, accidental trauma to a forelimb, to determine whether the growth of new connections plays a role in the reorganization of somatosensory cortex that occurs after major alterations in peripheral somatosensory inputs. In each monkey, microelectrode recordings of cortical areas 3b and 1 demonstrated massive reorganizations of the cortex related to the affected limb. Injections of tracers in area 1 of these monkeys revealed normal patterns of thalamocortical connections, but markedly expanded lateral connections in areas 3b and 1. Thus, the growth of intracortical but not thalamocortical connections could account for much of the reorganization of the sensory maps in cortex.

Structure and phase transitions of monolayers of intermediate-length n-alkanes on graphite studied by neutron diffraction and molecular dynamics simulation.

We present evidence from neutron diffraction measurements and molecular dynamics (MD) simulations of three different monolayer phases of the intermediate-length alkanes tetracosane (n-C(24)H(50) denoted as C24) and dotriacontane (n-C(32)H(66) denoted as C32) adsorbed on a graphite basal-plane surface. Our measurements indicate that the two monolayer films differ principally in the transition temperatures between phases. At the lowest temperatures, both C24 and C32 form a crystalline monolayer phase with a rectangular-centered (RC) structure. The two sublattices of the RC structure each consists of parallel rows of molecules in their all-trans conformation aligned with their long axis parallel to the surface and forming so-called lamellas of width approximately equal to the all-trans length of the molecule. The RC structure is uniaxially commensurate with the graphite surface in its [110] direction such that the distance between molecular rows in a lamella is 4.26 A=sqrt[3a(g)], where a(g)=2.46 A is the lattice constant of the graphite basal plane. Molecules in adjacent rows of a lamella alternate in orientation between the carbon skeletal plane being parallel and perpendicular to the graphite surface. Upon heating, the crystalline monolayers transform to a "smectic" phase in which the inter-row spacing within a lamella expands by approximately 10% and the molecules are predominantly oriented with the carbon skeletal plane parallel to the graphite surface. In the smectic phase, the MD simulations show evidence of broadening of the lamella boundaries as a result of molecules diffusing parallel to their long axis. At still higher temperatures, they indicate that the introduction of gauche defects into the alkane chains drives a melting transition to a monolayer fluid phase as reported previously.

Explanation and correction of false step heights in amplitude modulation atomic force microscopy measurements on alkane films.

We use a prototypical alkane film (n-C(32)H(66) or C32) adsorbed on a SiO(2) surface to compare step heights measured by amplitude modulation atomic force microscopy (AM-AFM) with those measured in the contact mode. The C32 film exhibits layers in which the molecules are oriented with their long axis parallel to the SiO(2) surface followed by partial layers of perpendicular molecules. We show that step heights measured in the AM and contact modes agree in all cases except where the step is between a surface formed by a layer of parallel molecules and one of perpendicular molecules. In this case, the AM mode gives a false step height that is as much as 20% lower than that measured in the contact mode and inferred from synchrotron X-ray specular reflectivity measurements. We propose that the weaker van der Waals forces between the AFM tip and a perpendicular layer compared to a parallel layer causes this discrepancy. We show how to correct the false step height by using the approximately linear relationship observed between phase angle (cantilever oscillation relative to the drive signal) and cantilever height measured in an approach curve.

Frequent loss of heterozygosity on the long arm of chromosome 6: identification of two distinct regions of deletion in childhood acute lymphoblastic leukemia.

Cytogenetic analysis of childhood acute lymphoblastic leukemia (ALL) identified nonrandom chromosomal abnormalities of the long arm of chromosome 6. Most of the alterations are deletions that are thought to be indicative of the presence of a tumor suppressor gene that is mutated on the remaining allele. These observations led us to consider whether 6q loss may contribute to the pathogenesis of childhood ALL. To define further a region containing this gene, we analyzed the loss of heterozygosity (LOH) of chromosome 6 in 113 primary ALL samples with matched normal DNA using 34 highly informative microsatellite markers. LOH was found in 17 (15%) samples at one or more of the loci, and partial or interstitial deletions of 6q were detected in 11 of these tumors. On the basis of these results, we performed a detailed deletional map and identified two distinct regions of deletion. The first region is flanked by D6S283 and D6S302 loci at 6q21-22. The second region is flanked by D6S275 and D6S283 loci at 6q21. Clinical analysis determined that LOH of 6q was demonstrated both in precursor-B cell ALLs (15 of 93; 16%) and in T cell ALLs (2 of 19; 11%). In addition, 19 patients have been studied at diagnosis and relapse; 18 showed the same 6q21-22 structural abnormality at relapse (normal, 16 patients; LOH, 2 patients) as their initial presentation, suggesting, albeit with a small patient sample size, that 6q21-22 deletions may be an initial event in leukemogenesis and may occur less frequently during the progression of childhood ALL. These data suggest the presence of putative tumor suppressor genes on chromosome arm 6q that are important in the development of both T and precursor-B childhood ALLs. Our map provides important information toward cloning putative ALL tumor suppressor genes.

Plasma free and total tryptophan, blood serotonin, and the hyperactivity syndrome: no evidence for the serotonin deficiency hypothesis.

Total and free plasma tryptophan and plasma cortisol levels were determined for children diagnosed as hyperactive or learning disabled and in normal siblings of these subjects. No differences were observed among the groups on any of the dependent variables related to a number of parameters measured for the hyperactive children such as degree of hyperactivity, presence of food allergies, favorable response to methylphenidate, and brain dysfunction. Moreover, in further comparisons no differences were found between hyperactive and age-matched controls on these variables as well as blood serotonin, nor were any differences found for a group of hyperactive children between placebo and methylphenidate trials. These data do not support earlier suggestions of a serotonin deficiency in hyperactive children.

Lung function in former intravenous drug abusers: the effect of ubiquitous cigarette smoking.

PURPOSE: To determine whether former intravenous drug abusers (IVDAs) demonstrate reductions in pulmonary function, especially in the diffusing capacity (DLCO), after adjustment for the effects of their ubiquitous smoking habit. Knowledge of baseline DLCO in this high-risk group is important in evaluating the effects of human immunodeficiency virus (HIV) and ensuing opportunistic infections. PATIENTS AND METHODS: Measurements of single-breath DLCO, forced vital capacity (FVC), and forced expiratory volume in 1 second (FEV1) were compared with predictive values that adjust for the effects of smoking. Patients were 98 ambulatory former IVDAs regularly attending a methadone maintenance program (62 men and 36 women; 94 current smokers, two ex-smokers, and two nonsmokers). RESULTS: When adjusted for smoking, FEV1 and DLCO were no different in the study sample than in cross sections of the general population: mean FEV1 105% predicted (men) and 97% predicted (women), mean DLCO 95% predicted (men) and 99% predicted (women). Eleven percent of the IVDAs had abnormal values for DLCO; only one subject had a value less than 50% of predicted. CONCLUSIONS: Most former IVDAs who regularly attend an ambulatory methadone program have normal DLCO values when the effects of smoking are taken into account. A decrease in DLCO in such subjects is presumptive evidence of superimposed disease, most likely related to opportunistic infections or HIV-associated malignancy or alveolitis.

Determination of sleep and wakefulness with the actigraph data analysis software (ADAS).

Current evidence has shown that, overall, actigraphy is an excellent tool for unobtrusive documentation of sleep/wake activity in normal individuals. However, a number of methodological issues remain to be resolved to warrant its use in clinical research. In this paper, we report the results of a study aimed at the development of a new scoring software that can accurately identify sleep and wakefulness. Using total sleep time as an index of comparison, the software was optimized on a calibration sample and prospectively tested on a validation sample. A strong correlation coefficient (r = 0.93, p < 0.008), with an average discrepancy value of 10 minutes, was observed for the calibration sample. The application of the optimal software to the validation sample revealed an even higher correlation coefficient (r = 0.97, p < 0.0001), with an average discrepancy value of 12 minutes.

An analysis of symptoms in patients with permanent ventricular pacemakers.

The prevalence and severity of symptoms of the "pacemaker syndrome" were investigated in 64 patients with VVI pacemakers and compared, in the same patients, to a series of control symptoms, unrelated to pacemaker function. Symptoms were also compared in patient groups unlikely to have the "pacemaker syndrome" (atrial fibrillation), most likely to have such symptoms (retrograde atrial activation) and in an intermediate group (competitive paced and sinus rhythms). There was a linear relationship between the frequency and severity of "pacemaker" symptoms and control questions in all groups and no preponderance of "pacemaker" symptoms in any group. The study provides an estimate of the number and severity of symptoms in patients with VVI pacemakers, demonstrates the non-specificity of the "pacemaker syndrome" and shows no evidence of a sub-clinical "pacemaker syndrome" in the patients observed.

Informed consent for research. Effects of readability, patient age, and education.

Comprehension of informed consent materials from a study of psychological variables associated with chest pain was evaluated as a function of age (27 to 69 years), education (5 to 20 years), and readability of information [low (college level) versus high (7th grade)]. The potentially confounding effect of memory was eliminated by allowing patients to use the written information sheets to find answers to the multiple choice test. Feedback and a repeat test were provided if any answers were incorrect. The findings indicated that comprehension varied inversely with age and directly with education. It is suggested that while ensuring informed consent may be difficult for all volunteers, it may be a critical problem for elderly patients with low education. The effects of readability were not consistent, suggesting that simplifying informed consent materials by shortening words and sentences may not, by itself, be sufficient to improve comprehension.

Withholding versus withdrawing life-sustaining treatment: patient factors and documentation associated with dialysis decisions.

OBJECTIVE: We evaluated prospectively the use of acute hemodialysis among hospitalized patients to identify demographic and clinical predictors of and chart documentation concerning dialysis withheld and withdrawn. DESIGN: Prospective cohort study. SETTING: Five teaching hospitals. PATIENTS: Five hundred sixty-five seriously ill hospitalized patients who had not previously undergone dialysis who developed renal failure. MAIN OUTCOME MEASURES: Patient demographics, clinical characteristics, preferences, and prognostic estimates associated with having dialysis withheld rather than initiated and withdrawn rather than continued. Differences in chart documentation concerning decision-making for dialysis withheld, withdrawn, and continued. RESULTS: Older patient age, cancer diagnosis, and male gender were associated with dialysis withheld rather than withdrawn. Age and gender differences persisted after adjustment for patients' aggressiveness of care preference. Worse 2-month prognosis was associated with both withholding and withdrawing dialysis. Chart documentation of decision-making was lacking more often for patients with dialysis withheld than for dialysis withdrawn. CONCLUSIONS: Measuring the equity of life-sustaining treatment use will require evaluation of care withheld, not just care withdrawn. Older patients and men, after accounting for prognosis and function, are more likely to have dialysis withheld than withdrawn after a trial. Further exploration is needed into this disparity and the inadequate chart documentation for patients with dialysis withheld.

Bladder distention therapy for symptomatic relief of frequency and urgency: a ten-year review.

OBJECTIVE: A retrospective review was undertaken to determine the efficacy of bladder distention therapy for the treatment of frequency and urgency, and to determine the relative value of prolonged versus short duration distention therapy. METHOD: Prolonged bladder distention therapy was performed on 14 patients and short duration distention on 8 patients over a ten-year period. Indications for the procedure included severe urgency, frequency, and incontinence from a variety of etiologies. RESULTS: Five of 14 patients (18 distentions, 2 bladder ruptures) who had prolonged distention, and 3 of 8 patients (9 distentions, 1 bladder rupture) who had short duration distention experienced symptomatic relief on follow-up (p > 0.7). Since there was no difference between the prolonged and short duration groups, the results were combined to yield 8 of 27 successful distentions (30%) in 8 of 22 patients (36%). All patients with detrusor hyperreflexia failed distention therapy. Complications included 3 cases of bladder rupture, 2 cases of urinary retention, and 1 case of urethral stricture. The rates of bladder rupture were identical in both groups (11%). CONCLUSIONS: The use of prolonged bladder distention therapy has no role in the treatment of detrusor hyperreflexia, and only limited success in the symptomatic relief of severe urgency, frequency, and incontinence of other etiologies. Equal efficacy of prolonged and short duration distention therapy would tend to favor the use of short duration distention to reduce possible anesthesia complications and cost.

Relationship between contraction and relaxation in human and rabbit corpus cavernosum.

Although alterations in corporeal smooth muscle tone undoubtedly play an important role in the etiology of erectile dysfunction, the relationship between the degree of corporeal smooth muscle contraction and the magnitude of the observed relaxation response has never been quantitated. Thus, in vitro studies were conducted to examine the relationship between alpha 1-adrenergic contractility, and relaxations elicited by the clinically and physiologically relevant vasorelaxants, nitroglycerin, nitroprusside, and prostaglandin E1. Corporeal tissues strips were isolated from impotent and potent men, as well as sexually mature rabbits, and precontracted over a wide range of phenylephrine doses, prior to exposure of each tissue to the same dose of vasorelaxant. Plots of percent contraction versus percent relaxation revealed that the relationship between contraction and relaxation was accurately described by a first order linear equation, and characterized by an inverse relationship in all tissues studied, for all vasorelaxants examined. Statistical analysis indicated that the slope of the regression line was significantly greater than unity in all corporeal tissues obtained from patients with organic impotence; however, corporeal tissues obtained from patients with documented erections and from sexually mature rabbits had significantly lower slopes that were indistinguishable from unity. The existence of an inverse relationship between contraction and relaxation, even in the absence of organic disease, emphasizes the importance of the level of basal corporeal smooth muscle tone per se. These studies provide further evidence implicating heightened adrenergic tone as a significant etiologic factor in erectile dysfunction.

Combined laparoscopic pelvic lymph node dissection and modified belt radical perineal prostatectomy for localized prostatic adenocarcinoma.

OBJECTIVE: Despite many known advantages, the radical perineal prostatectomy (RPP) had fallen out of favor because of the need for a second incision for the regional lymph node dissection. Laparoscopic lymphadenectomy, however, provides an accurate and minimally invasive alternative to open lymph node dissection. Herein are reported the practical advantages of combining laparoscopic lymph node dissection (LPLND) with RPP. METHODS: Forty-nine patients with clinically localized carcinoma of the prostate were considered candidates for RPP using a modified Belt technique. Thirty-five patients underwent attempted LPLND and 31 of these patients subsequently underwent RPP; 14 patients underwent RPP alone. Variables examined included total operative time, transfusion requirement, length of hospital stay, continence, and potency. RESULTS: The mean operative time for LPLND combined with RPP in 31 patients, including time for repositioning, was 4.5 hours (range 3.0 to 7.0 hours). Only 26 percent of the patients who underwent the combined approach required blood transfusions of which 75 percent received autologous units. Mean length of stay was six days, and laparoscopy did not contribute significantly to postoperative morbidity. Eighty-four percent of the patients are completely continent. Of 27 potent patients who underwent nerve-sparing surgery, 22 percent are potent and an additional 30 percent are sexually active with intracavernous pharmacotherapy. There were no perioperative deaths, 2 major complications, and 5 minor complications. CONCLUSIONS: Laparoscopic techniques now permit the urologist to utilize the perineal approach, and its many advantages, to radical prostatic extirpation without the need for a formal abdominal incision. The minimal blood loss and low morbidity associated with laparoscopic pelvic lymphadenectomy combined with the radical perineal prostatectomy make this procedure an attractive alternative to the open retropubic approach for clinically localized prostatic adenocarcinoma.

Temporal summation functions for detection of sine-wave gratings in young and older adults.

Temporal summation functions for 0.416 and 7.5 c/deg sinusoidal gratings were measured in young and old observers in order to test the hypothesis of a shift in sensitivity from "transient" to "sustained" channels in the aging visual system. Results failed to support the transient-shift hypothesis. Additional tests showed no age-related changes in temporal summation even within a single channel. When all observers were refracted for the test distance and matched for retinal illuminance, no age-related differences in contrast sensitivity were found.

Psychophysical evidence for losses in rod sensitivity in the aging visual system.

Rod sensitivity was measured with a criterion-free psychophysical method at 10 deg in the horizontal meridian of the nasal field of the left eye on 26 young (mean age, 24.1 yr) and 14 older (mean age 72.6 yr) observers in good ocular health. A 1 deg, 90 msec stimulus was delivered by means of a free-viewing optical system under computer control. Stimulus wavelengths were chosen to have either significant (406 nm) or minimal (560 nm) absorption by the older lens. After correction for senile miosis and lens density, 0.39 log unit higher thresholds for the older observers remained and are interpreted as being due to neural factors.

20-Cyclopropyl-cholecalciferol vitamin D3 analogs: a unique class of potent inhibitors of proliferation of human prostate, breast and myeloid leukemia cell lines.

We have synthesized and studied the ability of a series of nine novel 1,25 dihydroxyvitamin D3 [1,25(OH)2D3] analogs to inhibit clonal growth of myeloid leukemic cells (HL,60), prostate (LNCaP, PC-3 and DU-145) and breast (MCF-7) cancers cells. DU-145 cells were actively resistant to compounds (cmpd) with all of these modifications, but when we removed C-19 (E, 1,25-Dihydroxy-23E-ene-26,27-hexafluoro-19-nor-20-cyclopropy l- cholecalciferol) an analog resulted that was inhibitory against all three prostate cell lines, breast and HL-60 cell lines. Further analysis showed that pulse exposure (3 days, 10(-7) M) to this analog was enough to inhibit clonal growth of PC-3 cell by 50%. Furthermore, cmpd E increased the number of PC-3 cells in G1 and decreased the number in S phase. 1,25(OH)2D3 mediates its biological activities through specific binding to the vitamin D3 receptor (VDR) and subsequent association with vitamin D3 response elements (VDRE) in genes modulated by 1,25(OH)2D3. Several novel vitamin D3 cmpds have recently been identified which have 5- to 1000-fold greater abilities to induce differentiation and to inhibit proliferation of prostate cancer, breast cancer and HL-60 leukemic blast cells as compared to the parental 1,25(OH)2D3. To clarify the mechanism by which nine of these vitamin D3 analogs mediate their remarkably potent biological activities, we have investigated their abilities in PC-3 prostate cancer cells to transactivate a chroramphenicol acetyl transferase (CAT) reporter gene containing a VDRE from the human osteocalcin gene attached to a thymidine kinase minimal promoter. Dose-response studies of Cmpd E showed that in serumless culture conditions, transactivation of the VDRE-CAT was stronger than cmpd J [1,25(OH)2D3]. Then, we investigated the effects of vitamin D3 cmpd J in mice. Our data showed the growth inhibitory action of the vitamin D3 cmpd E in prostate cancer cell line (PC-3) was stastically superior to the non-treatment group in terms of tumor size and tumor weight in mice. In summary, this is the first report of a potent series of 20-cyclopropyl-cholecalciferol vitamin D3 analogs with the ability to inhibit proliferation of LNCaP, PC-3, DU-145, MCF-7 and HL-60 cell lines. These cmpds may mediate their potent anti-proliferative activities through a cell cycle arrest pathway.