Antiproliferative constituents in umbelliferae plants. IV. Constituents in the fruits of Anthriscus sylvestris Hoffm

The constituents in the fruit of Anthriscus sylvestris Hoffm. were investigated, and four lignans [deoxypodophyllotoxin, morelensin, (-)-deoxypodorhizone, and (-)-hinokinin], one phenylpropanoid [1-(3',4'-dimethoxyphenyl)-1 xi-hydroxy-2-propene], two phenylpropanoid esters [3',4'-dimethoxycinnamyl (Z)-2-angeloyloxymethyl-2-butenoate and 3',4'-dimethoxycinnamyl (Z)-2-tigloyloxymethyl-2-butenoate], and one polyacetylenic compound (falcarindiol) were isolated. Their antiproliferative activity against MK-1, HeLa and B16F10 cell lines is reported.     

Autosomal dominant hypophosphatemic rickets is linked to chromosome 12p13

Autosomal dominant hypophosphatemic rickets (ADHR) is an inherited disorder of isolated renal phosphate wasting, the pathogenesis of which is unknown. We performed a genome-wide linkage study in a large kindred to determine the chromosome location of the ADHR gene. Two-point LOD scores indicate that the gene is linked to the markers D12S314 [Z(theta) = 3.15 at theta = 0.0], vWf [Z(theta) = 5.32 at theta = 0.0], and CD4 [Z(theta) = 3.53 at theta = 0.0]. Moreover, multilocus analysis indicates that the ADHR gene locus is located on chromosome 12p13 in the 18-cM interval between the flanking markers D12S100 and D12S397. These data are the first to establish a chromosomal location for the ADHR locus and to provide a framework map to further localize the gene. Such studies will permit ultimate identification of the ADHR gene and provide further insight into phosphate homeostasis.     

Divinyl ethers and hydroxy fatty acids from three species of Laminaria (brown algae)

Three species of brown algae, Laminaria sinclairii, L. saccharina and L. setchellii, have been investigated for the presence of oxylipins. From one, L. sinclairii, three new divinyl ether fatty acids have been characterized as methyl ester derivatives (methyl 12-[1'(Z),3'(Z)-hexadienyloxy]-6(Z), 9(Z),11(E)-dodecatrienoate, methyl 12-[1'(Z),3'(Z)-hexadienyloxy]-9(Z), 11(E)-dodecadienoate, and methyl 14-[1'(Z),3'(Z)-hexadienyloxy]- 5(Z),8(Z),11(Z),13(E)-tetradecatetraenoate) by a variety of spectroscopic methods. In addition, one new [13(S)-hydroxy-6(Z),9(Z),11(E),15(Z)-octadecatetraenoic acid] and four known monohydroxy polyunsaturated fatty acids have been isolated from all three species as their methyl ester derivatives. The occurrence of these compounds in brown algae strongly suggests that these organisms possess an active lipoxygenase(s) with omega 6 specificity.     

Z-->B transition in poly[d(G-m5C)2] induced by interaction with 4',6-diamidino-2-phenylindole

The Z form of poly[d(G-m5C)2], in presence of Mg2+ ion, is found to be transformed into B form upon interaction with 4',6-diamidino-2-phenylindole (DAPI). The Z-->B transformation is complete at a mixing ratio of about 0.07 DAPI per DNA base pairs, i.e., each DAPI molecule may be related to the conversion of 6-7 base pairs. An interaction between DAPI and poly[d(G-m5C)2] in its Z form at low drug: DNA ratios is suggested from optical dichroism and time-resolved luminescence anisotropy results. The spectroscopic behaviour of DAPI indicates that the Z conformation of DNA does not provide normal binding sites for DAPI, such as groove or intercalation sites, but that the initial association may be of external nature.     

A pathway for biosynthesis of divinyl ether fatty acids in green leaves

[1-14C]alpha-Linolenic acid was incubated with a particulate fraction of homogenate of leaves of the meadow buttercup (Ranunculus acris L.). The main product was a divinyl ether fatty acid, which was identified as 12-[1'(Z),3'(Z)-hexadienyloxy]-9(Z),11(E)-dodecadienoic acid. Addition of glutathione peroxidase and reduced glutathione to incubations of alpha-linolenic acid almost completely suppressed formation of the divinyl ether acid and resulted in the appearance of 13(S)-hydroxy-9(Z), 11(E),15(Z)-octadecatrienoic acid as the main product. This result, together with the finding that 13(S)-hydroperoxy-9(Z), 11(E),15(Z)-octadecatrienoic acid served as an efficient precursor of the divinyl ether fatty acid, indicated that divinyl ether biosynthesis in leaves of R. acris occurred by a two-step pathway involving an omega6-lipoxygenase and a divinyl ether synthase. Incubations of isomeric hydroperoxides derived from alpha-linolenic and linoleic acids with the enzyme preparation from R. acris showed that 13(S)-hydroperoxy-9(Z),11(E)-octadecadienoic acid was transformed into the divinyl ether 12-[1'(Z)-hexenyloxy]-9(Z), 11(E)-dodecadienoic acid. In contrast, neither the 9(S)-hydroperoxides of linoleic or alpha-linolenic acids nor the 13(R)-hydroperoxide of alpha-linolenic acid served as precursors of divinyl ethers.     

“Meta-analysis of free-response studies, 1992–2008: Assessing the noise reduction model in parapsychology”: Correction to Storm, Tressoldi, and Di Risio (2010).

Reports an error in "Meta-analysis of free-response studies, 1992–2008: Assessing the noise reduction model in parapsychology" by Lance Storm, Patrizio E. Tressoldi and Lorenzo Di Risio (Psychological Bulletin, 2010[Jul], Vol 136[4], 471-485). In the article, the second to last sentence of the abstract (p. 471) was stated incorrectly. The sentence should read as follows: “The mean effect size value of the ganzfeld database was significantly higher than the mean effect size of the standard free-response database but was not higher than the effect size of the nonganzfeld noise reduction database.” (The following abstract of the original article appeared in record 2010-12718-001.) We report the results of meta-analyses on 3 types of free-response study: (a) ganzfeld (a technique that enhances a communication anomaly referred to as “psi”); (b) nonganzfeld noise reduction using alleged psi-enhancing techniques such as dream psi, meditation, relaxation, or hypnosis; and (c) standard free response (nonganzfeld, no noise reduction). For the period 1997–2008, a homogeneous data set of 29 ganzfeld studies yielded a mean effect size of 0.142 (Stouffer Z = 5.48, p = 2.13 × 10?8). A homogeneous nonganzfeld noise reduction data set of 16 studies yielded a mean effect size of 0.110 (Stouffer Z = 3.35, p = 2.08 × 10?4), and a homogeneous data set of 14 standard free-response studies produced a weak negative mean effect size of ?0.029 (Stouffer Z = ?2.29, p = .989). The mean effect size value of the ganzfeld database were significantly higher than the mean effect size of the nonganzfeld noise reduction and the standard free-response databases. We also found that selected participants (believers in the paranormal, meditators, etc.) had a performance advantage over unselected participants, but only if they were in the ganzfeld condition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Antimycobacterial matricaria esters and lactones from Astereae species

Six matricaria esters (MEs) and two matricaria lactones (MLs), isolated from members of the tribe Astereae (Asteraceae), were tested against Mycobacterium tuberculosis and M. avium, using a radiorespirometric bioassay. (2Z,8Z)-ME and (2E-8Z)-ME gave minimum inhibitory concentrations (MICs) of 50 micrograms ml-1 against M. tuberculosis and respective MICs of 25 and 50 micrograms ml-1 against M. avium. The (4Z,8Z)-ML, (2Z)-8-dehydro-ME and (2Z,8Z)-10-angeloyloxy-(2Z,8Z)-ME showed respective MICs of 12.5, 25, 25 micrograms ml-1 against M. tuberculosis and MICs of 50, 25, 25 micrograms ml-1 against M. avium, respectively. The MICs of (2Z,8Z)-10-tigloyloxy-ME and (2E,8Z)-10-angeloyloxy-ME and (4E,8Z)-ML ranged from 50 to > 100 micrograms ml-1 against both pathogenic mycobacteria.     

Investigating the Validity of Holland's (1959, 1997) RIASEC Typology Among Native Hawaiians.

The present study extends the literature base that is answering the call to examine the validity of J. L. Holland's (1959, 1997) 6 types of themes (realistic [R], investigative [I], artistic [A], social [S], enterprising [E], and conventional [C]) in his typology when applied to populations that are culturally different from the populations with whom the typology was developed. Native Hawaiians (N=156), a group not previously investigated, completed a personal demographics form and the Strong Interest Inventory (L. W. Harmon, J. C. Hansen, F. H. Borgen, & A. L. Hammer, 1994). The construct validity of Holland's typology was supported in that Holland's vocational interest types were arranged in a circular R-I-A-S-E-C order. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fracture of single crystals of the nickel-base superalloy PWA 1480E in helium at 22 °C

The fracture behavior of single crystals of the PWA 1480E nickel-base superalloy was studied using both scanning electron microscopy (SEM) and transmission electron microscopy (TEM) techniques. Notched single crystals with seven different crystal growth orientations near [100], [110], [111], [013], [112], [123], and [223] were tensile tested at 22 °C in a helium atmosphere at 34 MPa. Gamma prime particles were orderly and closely aligned with the cube edges along the [100], [010], and [001] directions of theγ matrix. The cuboid morphology of theγ’ precipitate was not influenced by the crystal growth orientation. The specimen with the [110] orientation was the strongest, while the crystal with the [100] orientation was the weakest. A stereoscopic technique, combined with the use of planary’ morphologies, was applied to identify the cleavage plane orientation. All specimens failed predominately by {lll}-type cleavage which originated from combined slip on various {111} planes. In most cases, deformation was found to occur inhomogeneously in intense slip bands lying on {111} planes and aligned parallel to the different slip directions. Both SEM and TEM studies indicated that {lll}-type slip was the controlling factor during cleavage fracture of single crystals of the PWA 1480E nickel-base superalloy. Formerly Graduate Student, Auburn University     

Effects of gavage versus dosed feed administration on the toxicokinetics of benzyl acetate in rats and mice

8-epi-prostaglandin F2 alpha stimulated contraction of human myometrial strips obtained from five different donors at the time of hysterectomy with a pEC50 value of 6.3 +/- 0.5. In paired strips from the same donors the pEC50 value for the selective TP receptor agonist U46619 ([1R-[1a,4a,5b(Z),6a(1E,3S*)]]-7-[6-(3- hydroxy-1-octenyl)-2-oxabicyclo[2.2.1]hept-5-yl]-5-heptenoic acid) was 8.3 +/- 0.4. In strips from four other donors 8-epi-prostaglandin F2 alpha was ineffective whereas the pEC50 for U46619 was 6.9 +/- 0.3. Responses to 8-epi-prostaglandin F2 alpha were unaffected by the selective DP receptor antagonist BW A868C (3-benzyl-5-(6-carboxyhexyl)-1-(2- cyclohexyl-2-hydroxyethylamino)hydantoin) at 50 nM but were blocked by the selective TP receptor antagonist L670596 ((-)6,8-difluoro-9-p-methylsulfonyl benzyl-1,2,3,4- tetrahydrocarbazol-1-yl-acetic acid) at 50 nM. The pIC50 values obtained when the TP receptor antagonists GR 32191 ([1R- [1 alpha(Z),2 beta,3 beta,5 alpha]]-(+)-7-[5-[[(1,1'-biphenyl)-4- yl]methoxy]-3-hydroxy-2-(1-piperidinyl)cyclopentyl]-4-heptenoic acid), ICI D1542 ((4(Z)-6-[(2S,4S,5R)-2-[1-methyl-1-(2-nitro-4-tolyloxy)ethyl]- 4-(3-pyridyl)-1,3-dioxan-5-yl]hex-4-enoic acid), ICI 192605 (4(Z)-6-[(2,4,5-cis)-2-(2-chlorophenyl)-4-(2-hydroxyphenyl)-1,3- dioxan-5-yl]hexenoic acid), L670596 and SQ 29548 ([1S-(1 alpha,2 beta(5Z),3 beta,4 alpha]]-7- [3-[[2-[(phenylamino)carbonyl]hydrazino]methyl]-7- oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid) were added cumulatively to strips pre-contracted with an EC80 concentration of 8-epi-prostaglandin F2 alpha were not significantly different from those obtained when an EC80 concentration of U46619 was used. The effects of 8-epi-prostaglandin F2 alpha on strips pre-contracted with an EC80 concentration of U46619 were not different from those of U46619 itself. It is concluded that in the non-pregnant human myometrium 8-epi-prostaglandin F2 alpha is a medium potency contractile agonist acting predominantly at the TP receptor.     

Early G1 growth arrest of hybridoma B cells by DMSO involves cyclin D2 inhibition and p21[CIP1] induction

Dimethylsulfoxide (DMSO) was shown to inhibit the proliferation of several B cell lines including Raji, Daudi, and SKW6-CL4 but the mechanisms involved in this growth arrest are still unclear. We show that in 7TD1 mouse hybridoma cells a DMSO-induced reversible G1 arrest involves inactivation of Rb kinases, cyclin D2/CDK4 and cyclin E/CDK2. This occurs by at least three distinct mechanisms. Inhibition of cyclin D2 neosynthesis leads to a dramatic decrease of cyclinD2/CDK4 complexes. This in turn enables the redistribution of p27[KIP1] from cyclin D2/CDK4 to cyclin E/CDK2 complexes. In addition, the simultaneous accumulation of p21[CIP1] entails increasing association with cyclin D3/CDK4 and cyclin E/CDK2. Thus, p21[CIP1] and p27[KIP1], act in concert to inhibit cyclin E/CDK2 activity which, together with CDK4 inactivation, confers a G1-phase arrest.     

Survival and recovery of Escherichia coli O157:H7 in inoculated bottled water

A methodology used to isolate Escherichia coli O157:H7 from water and survival of this pathogen in inoculated water is described. The methodology used in the isolation of E. coli O157:H7 included the use of selective plating on Sorbitol MacConkey agar (supplemented with potassium tellurite [2.5 mg/liter], cefixime [0.05 mg/liter], and cefsulodin [10 mg/liter], and modified hemorrhagic colitis agar (also supplemented with potassium tellurite [2.5 mg/liter]) and cefsulodin [10 mg/liter]). There were no significant differences (P < 0.05) between the recoveries of E. coli O157:H7 on these two selective media. Direct plating on these selective agars was used to determine the length of time that E. coli O157:H7 was able to grow, remain viable, and be resistant to the selective agents. E. coli O157:H7 survived in inoculated water for up to > 300 days, depending on the type of water. Observation by scanning electron microscopy indicated that E. coli O157:H7 cells attached to, and multiplied on, the container walls.     

High-dose treatment with lanreotide of patients with advanced neuroendocrine gastrointestinal tumors: clinical and biological effects

Pure geometric isomers of conjugated linoleic acid were prepared from castor oil as the primary starting material. Methyl octadeca-9Z,11E-dienoate (2) and methyl octadeca-9Z,11Z-dienoate (4) were obtained by zinc reduction of methyl santalbate (1, methyl octadec-11E-en-9-ynoate) and methyl octadec-11Z-en-9-ynoate (3), respectively, as the key intermediates. Methyl octadeca-9E,11E-dienoate (8) and methyl octadeca-9E,11Z-dienoate (9) were prepared by demesylation of the mesyloxy derivative of methyl ricinelaidate (6, methyl 12-hydroxy-octadec-9E-enoate). A study of the nuclear magnetic resonance spectral properties was carried-out, and the shifts of the olefinic carbon atoms of 18:2(9Z,11E) (2) and 18:2(9E,11Z) (9) were readily identified by a combination of incredible natural abundance double quantum transfer experiment, heteronuclear multiple bond correlation, and 1H-13C correlation spectroscopy correlation techniques. Doubts remain in the absolute identification of the individual olefinic carbon atoms of the 18:2(9Z,11Z) (4) and 18:2(9E,11E) (8), except the fact that the shifts of the "inner" (C-10 and C-11) and "outer" (C-9 and C-12) positioned olefinic carbon atoms of the conjugated diene system are distinguishable.     

Prediger's dimensional representation of Holland's RIASEC circumplex.

Conducted a structural meta-analysis to evaluate D. J. Prediger's (1982) 3-factor (1 general factor and 2 bipolar factors of data–ideas and things–people) representation of J. L. Holland's (1985) RIASEC circumplex (including 6 personality types: realistic [R], investigative [I], artistic [A], social [S], enterprising [E], and conventional [C]). Confirmatory factor analysis and multidimensional scaling were applied to 77 US RIASEC correlation matrices published between 1965 and 1989. Prediger's 3-factor model received support when predictions from his factor model conformed to the predictions from the circumplex. The presence and size of the general factor were confirmed, but the differential biasing effect of the general factor on the RIASEC structure was not supported. Although the uniqueness of the bipolar dimensions was not supported, these dimensions were found to be generalizable across S variables and several RIASEC inventories. It appears that the circumplex structure itself is the crucial distinguishing feature. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The bioactive conformation of aminoalkylindoles at the cannabinoid CB1 and CB2 receptors: insights gained from (E)- and (Z)-naphthylidene indenes

The aminoalkylindoles (AAIs) are agonists at both the cannabinoid CB1 and CB2 receptors. To determine whether the s-trans or s-cis form of AAIs is their receptor-appropriate conformation, two pairs of rigid AAI analogues were studied. These rigid analogues are naphthylidene-substituted aminoalkylindenes that lack the carbonyl oxygen of the AAIs. Two pairs of (E)- and (Z)-naphthylidene indenes (C-2 H and C-2 Me) were considered. In each pair, the E geometric isomer is intended to mimic the s-trans form of the AAIs, while the Z geometric isomer is intended to mimic the s-cis form. Complete conformational analyses of two AAIs, pravadoline (2) and WIN-55, 212-2 (1), and of each indene were performed using the semiempirical method AM1. S-trans and s-cis conformations of 1 and 2 were identified. AM1 single-point energy calculations revealed that when 1 and each indene were overlayed at their corresponding indole/indene rings, the (E)- and (Z)-indenes were able to overlay naphthyl rings with the corresponding s-trans or s-cis conformer of 1 with an energy expense of 1.13/0.69 kcal/mol for the C-2 H (E/Z)-indenes and 0.82/0.74 kcal/mol for the C-2 Me (E/Z)-indenes. On the basis of the hypothesis that aromatic stacking is the predominant interaction of AAIs such as 1 at the CB receptors and on the demonstration that the C-2 H (E/Z)- and C-2 Me (E/Z)-indene isomers can mimic the positions of the aromatic systems in the s-trans and s-cis conformers of 1, the modeling results support the previously established use of indenes as rigid analogues of the AAIs. A synthesis of the naphthylidene indenes was developed using Horner-Wittig chemistry that afforded the Z isomer in the C-2 H series, which was not produced in significant amounts from an earlier reported indene/aldehyde condensation reaction. This approach was extended to the C-2 Me series as well. Photochemical interconversions in both the C-2 H and C-2 Me series were also successful in obtaining the less favored isomer. Thus, the photochemical process can be used to provide quantities of the minor isomers C-2 H/Z and C-2 Me/E. The CB1 and CB2 affinities as well as the activity of each compound in the twitch response of the guinea pig ileum (GPI) assay were assessed. The E isomer in each series was found to have the higher affinity for both the CB1 and CB2 receptors. In the rat brain membrane assay versus [3H]CP-55,940, the Ki's for the C-2 H/C-2 Me series were 2.72/2.89 nM (E isomer) and 148/1945 nM (Z isomer). In membrane assays versus [3H]SR141716A, a two-site model was indicated for the C-2 H/C-2 Me (E isomers) with Ki's of 10. 8/9.44 nM for the higher-affinity site and 611/602 nM for the lower-affinity site. For the Z isomers, a one-site model was indicated with Ki's of 928/2178 nM obtained for the C2 H/C-2 Me analogues, respectively. For the C-2 H/C-2 Me series, the CB2 Ki's obtained using a cloned cell line were 2.72/2.05 nM (E isomer) and 132/658 nM (Z isomer). In the GPI assay, the relative order of potency was C-2 H E > C-2 Me E > C-2 H Z > C-2 Me Z. The C-2 H E isomer was found to be equipotent with 1, while the C-2 Me Z isomer was inactive at concentrations up to 3.16 microM. Thus, results indicate that the E geometric isomer in each pair of analogues is the isomer with the higher CB1 and CB2 affinities and the higher pharmacological potency. Taken together, results reported here support the hypothesis that the s-trans conformation of AAIs such as 1 is the preferred conformation for interaction at both the CB1 and CB2 receptors and that aromatic stacking may be an important interaction for AAIs at these receptors.     

The effect of anti-prolactin antibody on in vitro synthesis of a pregnancy-associated rat uterine glycoprotein

Experiments were conducted to study the hormonal (estrogen [E2], progesterone [P4] and prolactin [PRL]), regulation of synthesis of a pregnancy-associated glycoprotein (named Uterine Agglutinin or UA) in the Day 4 post coital (p.c.) rat uterus with antibody administration and immunohistochemistry. Of the antibodies used, it was shown that anti-PRL antibody was the most effective in reducing in vitro UA synthesis. The results suggested that in vitro UA synthesis could be correlated to serum PRL levels as analyzed by radio-immunoassay. Binding studies revealed that PRL bound specifically to the stromal cells of the rat uterus where UA is produced and localized.     

Identification of 5-keto-(7E,9E,11Z,14Z)-eicosatetraenoic acid as a novel nonenzymatic rearrangement product of leukotriene A4

Leukotriene A4 (LTA4), the reaction product of 5-lipoxygenase in human polymorphonuclear (PMN) leukocytes, is transformed both to LTB4 and a mixture of 5,6- and 5,12-dihydroxy-eicosatetraenoic acids (diHETE) via nonenzymatic hydrolysis. Evidence has been obtained that LTA4 is also converted to 5-keto-(7E,9E,11Z,14Z)-eicosatetraenoic acid (5-oxo-ETE). The compound was isolated from the products of the 5-lipoxygenase reaction and its structure elucidated by UV spectroscopy, LC-MS, two-dimensional [1H]NMR spectroscopy and chemical reduction to the corresponding alcohol. The 5-oxo-ETE represented about 14% of the LTA4 hydrolysis products as compared to 72 and 14% for the 5,12-diHETE and 5,6-diHETE, respectively. A similar profile of hydrolysis products was obtained after incubation of synthetic LTA4 in aqueous buffer. Human PMN leukocytes produced 5-oxo-ETE in an arachidonic acid-dependent and MK-886-inhibitable manner. The 5-oxo-ETE caused 50% inhibition of 5-lipoxygenase activity at 1 microM. These results demonstrate that the nonenzymatic conversion of LTA4, in addition to the previously described hydrolysis products, yields 5-oxo-ETE during both the 5-lipoxygenase reaction and arachidonic acid oxidation by human PMN leukocytes. They indicate that allylic epoxides can rearrange in aqueous media at physiological pH to spontaneously form beta,gamma-unsaturated ketones.     

Association of bone mineral density with apolipoprotein E phenotype

The phenotypes of apolipoprotein E (Apo E) and their relationship with the bone mineral density (BMD) were examined in 284 unrelated postmenopausal Japanese women aged 47-82 years (64.0 +/- 1.0 years, mean +/- SE). The Apo E phenotype was analyzed by the isoelectric focusing method, followed by immunoblotting. The relationship between the Apo E phenotype and the vitamin D receptor (VDR) gene or estrogen receptor (ER) gene genotypes was also studied in the same population. The Apo E phenotypic frequencies in our population were 9.9% for E3/2, 66.5% for E3/3, 1.8% for E4/2, 19.7% for E4/3, and 2.1% for E4/4. We classified these phenotypes into three categories: Apo E4-/- (E3/2 and E3/3, n = 217, Apo E4 +/- (E4/3 and E4/2, n = 61), and Apo E4+/+ (E4/4, n = 6). The age, body weight, body height, and years since menopause were not significantly different among these three categories. The lumbar BMD values in these three groups were significantly different in the order of E4-/- (0.91 +/- 0.01 g/cm2), E4 +/- (0.85 +/- 0.02 g/cm2), and E4+/+ (0.83 +/- 0.06 g/cm2) (p = 0.031). The same trend was also observed for the Z score of the total BMD (p = 0.022). The serum level of intact osteocalcin in E4+/+ (15.2 +/- 5.7 ng/ml) was higher than in E4-/- (7.7 +/- 0.3 ng/ml) or E4 +/- (7.7 +/- 0.7 ng/ml) (p = 0.004 by analysis of variance). However, there were no other significant differences in the serum or urinary levels of bone turnover markers. Serum cholesterol in the E4+/+ group tended to be higher than in the other two groups (p = 0.05). There were no significant associations of the VDR and ER genotypes with the Apo E4 phenotype. A multivariate linear regression analysis revealed Apo E4 to be a significant, independent predictor of the Z score of the lumbar BMD. The effect of the Apo E4 allele on the Z score of the lumbar BMD (-0.493 +/- 0.152) was not significantly different from that in the AAB of VDR (-0.616 +/- 0.225) or PPxx of ER (-0.785 +/- 0.314). In conclusion, the Apo E4 allele is associated with a low bone mass in postmenopausal Japanese.     

Opposite trends of changes in reactive behaviours of macrophages and astrocytes following gamma-irradiation performed at different stages of prenatal development. A study in the injured brain of 6-day-old rat

Pregnant Wistar rats were exposed to a single 1.0 Gy dose of gamma rays on gestational days 13, 15, 17 or 19 (E13s, E15s, E17s and E19s, respectively). A mechanical injury was made in the cerebral hemisphere of their 6 day-old male offsprings. The injured rats were injected with [3H] thymidine on day 1 or 2 after injury and killed 4 h after the injection. Brain sections were processed for BSI-B4 isolectin histochemistry, subjected to autoradiography and examined microscopically to record numbers of proliferating and unproliferating macrophages located within the region of injury. The total number of macrophages as well as number of their divisions were minimal in E13s then showed a regular increase in E15s and E17s, and reached its maximal level in brains irradiated on E19. The trend of changes was opposite to that showed by changes in the intensity of astrocyte proliferation [Z. Setkowicz, K. Janeczko, Effects of prenatal gamma-irradiation on the astrocyte proliferation in response to injury in the brain of 6-day-old rat, Brain Res. 803 (1998) 122-128.]. The recruitment and proliferation of macrophages and the astrocyte proliferation were regarded as reactive processes occurring under control of different regulatory mechanisms acting within the region of injury.